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Gustavsson, Inger M.
Alternative names
Publications (10 of 28) Show all publications
Gustavsson, I. M., Aarnio, R., Myrnäs, M., Lindberg, J. H., Taku, O., Meiring, T., . . . Gyllensten, U. B. (2019). Clinical validation of the HPVIR high-risk HPV test on cervical samples according to the international guidelines for human papillomavirus DNA test requirements for cervical cancer screening. Virology Journal, 16(1), Article ID 107.
Open this publication in new window or tab >>Clinical validation of the HPVIR high-risk HPV test on cervical samples according to the international guidelines for human papillomavirus DNA test requirements for cervical cancer screening
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2019 (English)In: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 16, no 1, article id 107Article in journal (Refereed) Published
Abstract [en]

Background

The indicating FTA card is a dry medium used for collection of cervical samples. HPVIR is a multiplex real-time PCR test that detects 12 high-risk human papillomavirus types (hrHPV) and provides single genotype information for HPV16, − 31, − 35, − 39, − 51, − 56, and − 59 and pooled type information for HPV18/45 and HPV33/52/58. The aim of this study was to evaluate whether a strategy with cervical samples collected on the FTA card and subsequently analysed with the HPVIR test complies with the criteria of the international guidelines for a clinically validated method for cervical screening.

Methods

We performed a non-inferiority test comparing the clinical sensitivity and specificity of the candidate test (FTA card and HPVIR) with a clinically validated reference test (Cobas® HPV test) based on liquid-based cytology (LBC) samples. Two clinical samples (LBC and FTA) were collected from 896 participants in population-based screening. For evaluation of the specificity we used 799 women without ≥ CIN2, and for clinical sensitivity we used 67 women with histologically confirmed ≥ CIN2. The reproducibility was studied by performing inter- and intra-laboratory tests of 558 additional clinical samples.

Results

The clinical sensitivity and specificity for samples collected on the FTA card and analysed using the HPVIR test were non-inferior to samples analysed with the Cobas® HPV test based on LBC samples (non-inferiority test score, p = 1.0 × 10− 2 and p = 1.89 × 10− 9, respectively). Adequate agreement of > 87% was seen in both the intra- and inter-laboratory comparisons.

Conclusions

Samples collected on the indicating FTA card and analysed with HPVIR test fulfil the requirements of the international guidelines and can therefore be used in primary cervical cancer screening.

Keywords
HPV, DNA testing, Primary cervical cancer screening, International guidelines
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-394268 (URN)10.1186/s12985-019-1216-7 (DOI)000483382500001 ()31438976 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Cancer Society
Available from: 2019-10-09 Created: 2019-10-09 Last updated: 2019-10-09Bibliographically approved
Aarnio, R., Wikström, I., Gustavsson, I. M., Gyllensten, U. B. & Olovsson, M. (2019). Diagnostic excision of the cervix in women over 40 years with human papilloma virus persistency and normal cytology. European journal of obstetrics & gynecology and reproductive biology: X, 3, Article ID 100042.
Open this publication in new window or tab >>Diagnostic excision of the cervix in women over 40 years with human papilloma virus persistency and normal cytology
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2019 (English)In: European journal of obstetrics & gynecology and reproductive biology: X, ISSN 2590-1613, Vol. 3, article id 100042Article in journal (Refereed) Published
Abstract [en]

Objective: Persistent infection with human papillomavirus (HPV) is recognized as the main risk factor of cervical cancer. Investigation via cytology and colposcopy have lower sensitivity than HPV testing in the diagnosis of high-grade cervical intraepithelial neoplasia (CIN2+). Despite normal cytology and colposcopy findings women with persistent HPV infection have an increased risk of CIN2+. The aim of the study was to evaluate the proportion of histologically confirmed CIN2+ in women with persistent HPV infection and normal Pap smears.

Study design: From April 2013 until March 2016 we prospectively recruited 91 women over 40 years with persistent HPV infection without any abnormalities in cytology. Of these, 40 women attended a gynecological examination including an HPV test, Pap smear, endocervical cytology, colposcopy with biopsies and diagnostic loop electrosurgical excision procedure (LEEP). Biopsy and LEEP samples were subjected to histological examination.

Results: CIN2+ was verified by histological examination of the LEEP sample in 6/40 (15%) of the women. All the cytological samples were normal and none of the biopsies confirmed CIN2+. Only 19/40 women still had a persistent HPV infection at the study visit. None of the 21/40 women who had cleared their HPV infection at the study visit had CIN2+ in histology of the LEEP sample.

Conclusions: A persistent HPV infection needs to be monitored despite normal Pap smears, since 6/40 (15%) women older than 40 years, was revealed to have an undiagnosed CIN2+ when LEEP was performed. Counseling women regarding the risk of cervical cancer and the expected effect of an eventual LEEP can help them to make an optimal informed choice.

Keywords
Cervical intraepithelial neoplasia, Colposcopy, Human papillomavirus, Loop electrical excision procedure, Transformation zone
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-400770 (URN)10.1016/j.eurox.2019.100042 (DOI)31404426 (PubMedID)
Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-03-18Bibliographically approved
Berggrund, M., Gustavsson, I. M., Aarnio, R., Lindberg, J. H., Sanner, K., Wikström, I., . . . Gyllensten, U. B. (2019). HPV viral load in self-collected vaginal fluid samples as predictor for presence of cervical intraepithelial neoplasia.. Virology Journal, 16, Article ID 146.
Open this publication in new window or tab >>HPV viral load in self-collected vaginal fluid samples as predictor for presence of cervical intraepithelial neoplasia.
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2019 (English)In: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 16, article id 146Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: This study was performed to evaluate the use of high-risk HPV (hrHPV) viral load in screening tests for cervical cancer to predict persistent infection and presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+).

METHODS: We followed women between 30 and 60 years of age who performed self-sampling of vaginal fluid and subsequently a hrHPV test. Women who were hrHPV positive in their screening test repeated the hrHPV test 3-6 months later and were included in the present study.

RESULTS: Our results show that women with a persistent HPV16 infection had higher HPV viral load in their primary screening test than women with transient infections (p = 5.33e-03). This was also true for sum of viral load for all hrHPV types in the primary screening test (p = 3.88e-07). 48% of women with persistent HPV16 infection and CIN2+ had an increase in HPV16 titer in the follow-up test, as compared to only 20% of women with persistent infection but without CIN2+ lesions. For the sum of all hrHPV types, 41% of women with persistent infection and CIN2+ had an increase in titer as compared to 26% of women without CIN2 + .

CONCLUSIONS: The results show that hrHPV viral load in the primary screening HPV test is associated with the presence of CIN2+ and could be used in triaging hrHPV positive women for different follow-up strategies or recall times. Serial testing of hrHPV viral load has the potential to distinguish women with CIN2+ lesions from women with persistent infection but without CIN2+ lesions.

Keywords
CIN2+, Cervical cancer, HPV viral load, Self-sampling, hrHPV
National Category
Obstetrics, Gynecology and Reproductive Medicine Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-406972 (URN)10.1186/s12985-019-1253-2 (DOI)000513831600002 ()31771594 (PubMedID)
Funder
Swedish Cancer SocietySwedish Foundation for Strategic Research Swedish Research Council
Available from: 2020-03-17 Created: 2020-03-17 Last updated: 2020-03-20Bibliographically approved
Cui, T., Enroth, S., Ameur, A., Gustavsson, I., Lindquist, D. & Gyllensten, U. (2019). Invasive cervical tumors with high and low HPV titer represent molecular subgroups with different disease etiology. Carcinogenesis, 40(2), 269-278
Open this publication in new window or tab >>Invasive cervical tumors with high and low HPV titer represent molecular subgroups with different disease etiology
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2019 (English)In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 40, no 2, p. 269-278Article in journal (Refereed) Published
Abstract [en]

Invasive cervical cancer (ICC) with very low titer of high-risk human papillomavirus (HPV) has worse clinical outcome than cases with high titer, indicating a difference in molecular etiology. Fresh-frozen ICC tumors (n = 49) were classified into high- and low-HPV-titer cases using real-time PCR-based HPV genotyping. The mutation spectra were studied using the AmpliSeq Comprehensive Cancer Panel and the expression profiles using total RNA sequencing, and the results were validated using the AmpliSeq Transcriptome assay. HPV DNA genotyping and RNA sequencing showed that 16.6% of ICC tumors contained very low levels of HPV DNA and HPV transcripts. Tumors with low HPV levels had more mutations with a high allele frequency and fewer mutations with low allele frequency relative to tumors with high HPV titer. A number of genes showed significant expression differences between HPV titer groups, including genes with somatic mutations. Gene ontology and pathway analyses implicated the enrichment of genes involved in DNA replication, cell cycle control and extracellular matrix in tumors with low HPV titer. The results indicate that in low titer tumors, HPVs act as trigger of cancer development whereas somatic mutations are clonally selected and become drivers of the tumor development process. In contrast, in tumors with high HPV titer the expression of HPV oncoproteins plays a major role in tumor development and the many low frequency somatic mutations represent passengers. This putative subdivision of invasive cervical tumors may explain the higher radiosensitivity of ICC tumors with high HPV titer and thereby have consequences for clinical management.

National Category
Cell and Molecular Biology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-388612 (URN)10.1093/carcin/bgy183 (DOI)000472792800012 ()30596972 (PubMedID)
Funder
Swedish Cancer Society, CF23560Swedish Research Council, 2012-2884Swedish Society for Medical Research (SSMF)Knut and Alice Wallenberg Foundation, KAW2011.0205
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2019-07-02 Created: 2019-07-02 Last updated: 2019-08-23Bibliographically approved
Gustavsson, I. M., Aarnio, R., Berggrund, M., Lindberg, J. H., Sanner, K., Wikström, I., . . . Gyllensten, U. B. (2019). Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel.. International Journal of Cancer, 144(1), 89-97
Open this publication in new window or tab >>Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel.
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 1, p. 89-97Article in journal (Refereed) Published
Abstract [en]

We conducted a randomised study to compare vaginal self-sampling with assisted sampling by medical personnel on the cervix for HPV testing in primary screening. The first aim was to determine if the HPV prevalence is independent of sampling location (vagina versus cervix) and the person performing the sampling. The second aim was to evaluate if the two sampling strategies differed in the detection rate of CIN2+. In total, 19,523 women were randomised into two groups, with 9926 invited to perform self-sampling (SS arm) using the Rover VIBA-brush and 9597 offered assisted sampling using the cytobrush (AS arm). All samples were applied to the indicating FTA elute card and analysed for high-risk HPV using the hpVIR real-time PCR assay. The outcome for the first aim was HPV prevalence and for the second aim the number of CIN2+ based on histology. In the SS arm, 52.7% of invited women participated in the study, as compared to 34.2% in the AS arm. All samples contained sufficient amount of nuclear DNA for a valid HPV result, with vaginal samples having a higher DNA amount than cervical samples (p < 4.62 × 10-11 ). HPV prevalence was 4.6% in the SS arm and 4.1% in the AS arm (p = 5.5 × 10-2 ), and the distribution of HPV types similar between arms. There was no difference in the prevalence of CIN2+ per 1000 women screened between arms (p = 0.86). The results show that vaginal self-sampling is an equivalent alternative to sampling by medical personnel for HPV typing and identification of CIN2+.

Keywords
HPV test, cervical cancer, randomised study, screening, self-sampling
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-367086 (URN)10.1002/ijc.31637 (DOI)000451479900009 ()29943822 (PubMedID)
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Swedish Cancer Society
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2020-03-18Bibliographically approved
Lindström, A., Sanchez Hermansson, R., Gustavsson, I. M., Lindberg, J. H., Gyllensten, U. B. & Olovsson, M. (2018). Cervical dysplasia in elderly women performing repeated self-sampling for HPV testing. PLoS ONE, 13(12), Article ID e0207714.
Open this publication in new window or tab >>Cervical dysplasia in elderly women performing repeated self-sampling for HPV testing
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0207714Article in journal (Refereed) Published
Abstract [en]

Background About 30% of the cervical cancer cases in Sweden occur in women older than 60. The primary aim was to evaluate the acceptability of repeated self-sampling at home for HPV-testing in elderly women. The prevalence of HPV and HPV related dysplasia as well as the sensitivity of cytology was evaluated. Methods Repeated self-sampling at home for HPV testing was offered 375 women in each of the four age groups 60, 65, 70 and 75 years. Women with two consecutive positive HPV tests were examined with sampling for histology and cytology. Findings A self-sample was provided by 59.5% (893/1500) of the invited women. The overall prevalence of HPV was 4.4% (95% CI 3.2-6.0, n = 39) in the first test, and 2.5% were persistent positive in the second test (95% C 1.6-3.8, n = 22) collected on average 5.5 months later. Dysplasia, was found in 1.8% (16/893) (95% CI 1.1-3.0) and CIN 2+ in 1.0% (9/893) (95% CI 0.5-2.0) of the women. Of the 16 women with dysplasia in histology, 13 (81.2%) had a normal cytology. Interpretation Repeated self-sampling at home combined with HPV testing was well accepted among elderly women. A high prevalence of CIN was diagnosed by histology. Cytology showed extremely low sensitivity and should not be recommended for this age group.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-372761 (URN)10.1371/journal.pone.0207714 (DOI)000452212400061 ()30517176 (PubMedID)
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-01-14Bibliographically approved
Gustavsson, I. M., Aarnio, R., Berggrund, M., Lindberg, J. H., Strand, A.-S., Sanner, K., . . . Gyllensten, U. B. (2018). Randomised study shows that repeated self-sampling and HPV test has more than two-fold higher detection rate of women with CIN2+ histology than Pap smear cytology. British Journal of Cancer, 118(6), 896-904
Open this publication in new window or tab >>Randomised study shows that repeated self-sampling and HPV test has more than two-fold higher detection rate of women with CIN2+ histology than Pap smear cytology
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2018 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 118, no 6, p. 896-904Article in journal (Refereed) Published
Abstract [en]

Background:

This randomised study compared the detection rate of cervical intraepithelial neoplasia-positive (CIN2+) based on histology in women performing repeated self-sampling of vaginal fluid (VF) for human papillomavirus (HPV) test with a control group following the ordinary screening by Pap smear cytology.

Methods:

36390 women aged 30–49 years scheduled for invitation to organised screening were randomised in two groups, one to perform self-sampling of VF for HPV test (n=17 997, HPV arm) and the other group to perform screening by PAP smear cytology (n=18 393, control arm). HPV positive women in the HPV arm repeated the self-sampling and the HPV test on average 4.4 months later and those with two consecutive positive HPV tests were referred to colposcopy. Outcome was CIN2+ based on histology during 18-month follow-up.

Results:

Participation rate was 47% in the HPV arm and 39% in the control arm. The HPV prevalence in the first self-sampling was 6.9%, and 71% of these women were HPV positive in their second test. For the per-protocol approach, cumulative prevalence of histological CIN2+ in the HPV arm was 20.2 per 1000 women screened as compared to 10.8 in the control arm. The cumulative prevalence of CIN2+ diagnosed per 1000 years screened was 160.8 in the HPV arm as compared with 25.4 in the control arm.

Conclusions:

Repeated self-sampling of VF and HPV test had more than a two-fold higher discovery rate of CIN2+ per 1000 women screened as compared with PAP smear cytology.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-367087 (URN)10.1038/bjc.2017.485 (DOI)000427945800030 ()29438367 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Cancer SocietySwedish Society for Medical Research (SSMF)
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2020-03-18Bibliographically approved
Sanner, K., Wikström, I., Gustavsson, I., Wilander, E., Lindberg, J. H., Gyllensten, U. & Olovsson, M. (2015). Daily self-sampling for high-risk human papillomavirus (HR-HPV) testing.. Journal of Clinical Virology, 73, 1-7
Open this publication in new window or tab >>Daily self-sampling for high-risk human papillomavirus (HR-HPV) testing.
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2015 (English)In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 73, p. 1-7Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Self-sampling for HPV as part of primary screening is a well-tolerated method for women not attending organized Pap smear screening and could increase coverage of cervical cancer screening.

OBJECTIVE: To investigate if the prevalence of HR-HPV varies from day to day in infected women and if one single sample is reliable for detecting an ongoing infection.

STUDY DESIGN: This is a prospective cohort study on 12 premenopausal and 13 postmenopausal women performing daily self-sampling for HR-HPV testing. They were all HR-HPV-positive 1-3 months ago. Postmenopausal women were sampled for 28 days and premenopausal women sampled during bleeding-free days in one menstrual cycle. A possible difference in viral load between the estrogen-dominated proliferative phase and the progesterone-dominated secretory phase was analyzed.

RESULTS AND CONCLUSIONS: Consistent results throughout the sampling period were observed for 19 women, with either a daily presence of HPV (14 women) or no HPV at all during the sampling period (5 women). Of 607 samples from 25 women, 596 were consistently positive or negative for HPV during the sampling period and 11 were inconsistent (2%). There was no difference in HPV copy number between the estrogen dominated proliferative or progesterone dominated secretory menstrual cycle phases. The major finding was a high degree of consistency concerning HR-HPV positivity and negativity of HR-HPV in vaginal fluid during a sustained period of daily self-sampling. It does not appear to matter whether the sample is collected in the proliferative or secretory phase.

Keywords
Cervical cancer; Human papilloma virus (HPV); Self-sampling; Repeated sampling; Screening
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-272544 (URN)10.1016/j.jcv.2015.09.016 (DOI)000367390700001 ()26498105 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer Society
Available from: 2016-01-14 Created: 2016-01-14 Last updated: 2017-11-30Bibliographically approved
Ameur, A., Meiring, T. L., Bunikis, I., Häggqvist, S., Lindau, C., Lindberg, J. H., . . . Gyllensten, U. (2014). Comprehensive profiling of the vaginal microbiome in HIV positive women using massive parallel semiconductor sequencing. Scientific Reports, 4, 4398
Open this publication in new window or tab >>Comprehensive profiling of the vaginal microbiome in HIV positive women using massive parallel semiconductor sequencing
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2014 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, p. 4398-Article in journal (Refereed) Published
Abstract [en]

Infections by HIV increase the risk of acquiring secondary viral and bacterial infections and methods are needed to determine the spectrum of co-infections for proper treatment. We used rolling circle amplification (RCA) and Ion Proton sequencing to investigate the vaginal microbiome of 20 HIV positive women from South Africa. A total of 46 different human papillomavirus (HPV) types were found, many of which are not detected by existing genotyping assays. Moreover, the complete genomes of two novel HPV types were determined. Abundance of HPV infections was highly correlated with real-time PCR estimates, indicating that the RCA-Proton method can be used for quantification of individual pathogens. We also identified a large number of other viral, bacterial and parasitic co-infections and the spectrum of these co-infections varied widely between individuals. Our method provides rapid detection of a broad range of pathogens and the ability to reconstruct complete genomes of novel infectious agents.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-223522 (URN)10.1038/srep04398 (DOI)000332937300007 ()
Available from: 2014-04-30 Created: 2014-04-22 Last updated: 2017-12-05Bibliographically approved
Andersson, S., Mints, M., Gyllensten, U., Lindell, M., Gustavsson, I., Lambe, M. & Wilander, E. (2014). Uneven distribution of human papillomavirus 16111 cervical carcinoma in situ and squamous cell carcinoma in older females: A retrospective database study. Oncology Letters, 8(4), 1528-1532
Open this publication in new window or tab >>Uneven distribution of human papillomavirus 16111 cervical carcinoma in situ and squamous cell carcinoma in older females: A retrospective database study
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2014 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 8, no 4, p. 1528-1532Article in journal (Refereed) Published
Abstract [en]

Human papillomavirus (HPV) 16 is the dominant cofactor in cervical cancer development. The present report investigated the age-specific prevalence of HPV16 in cervical carcinoma in situ (CIS) in females attending organised cervical cancer screening. A retrospective observational study was performed based on individual data from two databases. A total of 162 females aged between 20 and 65 years from Uppsala County, Sweden with CIS and an HPV test conducted between 2010 and 2011, preceding or concomitant to CIS diagnosis, were included. Females with cervical squamous cell carcinoma (SCC; n=35) were used for comparison. In total, 96% (n=156) of females with CIS were positive for high-risk HPV; HPV16 was the most prevalent (44.5%), followed by HPV33/52/58 (19.5%), HPV31 (13.1%) and HPV18145 (9.5%). HPV16 was most frequently detected in females with CIS aged between 20 and 29 years (73.6%) and least frequently detected in those aged between 50 and 65 years (33.3%), with a statistically significant age-specific difference (P=0.001). Among the HPV16-positive females, multiple infections were most frequent in the younger age groups. The prevalence of HPV16 in females with CIS decreased with age, whereas a high prevalence of HPV16 remained in females with SCC. These results may indicate that HPV16 has increased oncogenic potential in older females.

Keywords
cervix, carcinoma in situ, human papillomavirus 16, prevalence, old age
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-235626 (URN)10.3892/ol.2014.2347 (DOI)000342725400023 ()
Available from: 2014-11-11 Created: 2014-11-06 Last updated: 2017-12-05Bibliographically approved
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