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Zhang, Y., Zhou, C. K., Rencsok, E. M., Fall, K., Lotan, T. L., Loda, M., . . . Ebot, E. M. (2019). A prospective study of intraprostatic inflammation, focal atrophy, and progression to lethal prostate cancer. Cancer Epidemiology, Biomarkers and Prevention, Article ID cebp.0713.2019.
Open this publication in new window or tab >>A prospective study of intraprostatic inflammation, focal atrophy, and progression to lethal prostate cancer
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2019 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, article id cebp.0713.2019Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: Inflammation and focal atrophy are common features adjacent to prostate tumors. Limited evidence exists on whether these features have prognostic significance.

METHODS: In the Health Professionals Follow-Up Study and Physicians' Health Study, we studied 1,035 men diagnosed with prostate cancer. A genitourinary pathologist centrally reviewed tumor and normal areas of hematoxylin and eosin slides from prostate cancer specimens for the presence of acute and chronic inflammation, and four subtypes of focal atrophy. Cox proportional hazards models adjusted for potential confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of these features with lethal prostate cancer, defined as development of metastatic disease or death during follow-up.

RESULTS: During a median of 12 years of follow-up, 153 men developed lethal prostate cancer. Eighty-four percent of men had histologic evidence of chronic inflammation and 30% had acute inflammation. Both chronic and acute inflammation were inversely associated with lethal prostate cancer in age- and lifestyle-adjusted models. Chronic inflammation remained inversely associated with lethal prostate cancer after additionally adjusting for prognostic clinical features (HR=0.45, 95% CI 0.30 to 0.69 for mild, HR=0.51, 95% CI 0.33 to 0.80 for moderate to severe). None of the atrophic lesions were associated with lethal prostate cancer.

CONCLUSIONS: Our data suggest that the presence of inflammation, particularly chronic inflammation, in prostate cancer tissue is associated with better prognosis among prostate cancer patients.

IMPACT: This is the largest prospective cohort study to examine the association between inflammation, focal atrophy, and lethal prostate cancer.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-76639 (URN)10.1158/1055-9965.EPI-19-0713 (DOI)31533941 (PubMedID)
Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2019-09-24Bibliographically approved
Kantor, E. D., Udumyan, R., Giovannucci, E. L., Valdimarsdottir, U. A., Signorello, L. B., Montgomery, S. & Fall, K. (2019). Association of Blood Marker of Inflammation in Late Adolescence With Premature Mortality. JAMA pediatrics
Open this publication in new window or tab >>Association of Blood Marker of Inflammation in Late Adolescence With Premature Mortality
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2019 (English)In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211Article in journal (Refereed) Epub ahead of print
Place, publisher, year, edition, pages
American Medical Association, 2019
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:oru:diva-76166 (URN)10.1001/jamapediatrics.2019.2835 (DOI)31479147 (PubMedID)
Available from: 2019-09-10 Created: 2019-09-10 Last updated: 2019-09-10Bibliographically approved
Udumyan, R., Montgomery, S., Fang, F., Valdimarsdóttir, U., Hardardottir, H., Ekbom, A., . . . Fall, K. (2019). Beta-blocker use and lung cancer mortality in a nationwide cohort study of patients with primary non-small cell lung cancer. Cancer Epidemiology, Biomarkers and Prevention, Article ID cebp.0710.2019.
Open this publication in new window or tab >>Beta-blocker use and lung cancer mortality in a nationwide cohort study of patients with primary non-small cell lung cancer
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2019 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, article id cebp.0710.2019Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: Beta-adrenergic receptor blockers have been associated with improved survival among patients with different types of malignancies, but available data for non-small cell lung cancer (NSCLC) patients is contradictory and limited to small hospital-based studies. We therefore aimed to investigate if β-blocker use at the time of cancer diagnosis is associated with lung cancer mortality in the largest general population-based cohort of patients with NSCLC to date.

PATIENTS AND METHODS: For this retrospectively defined nationwide cohort study, we used prospectively collected data from Swedish population and health registers. Through the Swedish Cancer Register, we identified 18,429 patients diagnosed with a primary NSCLC between 2006 and 2014 with follow-up to 2015. Cox regression was used to estimate the association between beta-blocker use at time of cancer diagnosis ascertained from the Prescribed Drug Register and cancer-specific mortality identified from the Cause of Death Register.

RESULTS: Over a median follow-up of 10.2 months, 14,994 patients died (including 13,398 from lung cancer). Compared with non-use, beta-blocker use (predominantly prevalent use, 93%) was not associated with lung cancer mortality [hazard ratio (95% confidence interval): 1.01 (0.97-1.06)]. However, the possibility that diverging associations for specific beta-blockers and some histopathological subtypes exist cannot be excluded.

CONCLUSION: In this nationwide cohort of NSCLC patients, beta-blocker use was not associated with lung cancer mortality when assessed in aggregate in the total cohort, but evidence for some beta-blockers is less conclusive.

IMPACT: Our results do not indicate that beta-blocker use at lung cancer diagnosis reduces the cancer-specific mortality rate in NSCLC patients.

Place, publisher, year, edition, pages
Prevention American Association for Cancer Research, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-77618 (URN)10.1158/1055-9965.EPI-19-0710 (DOI)31641010 (PubMedID)
Available from: 2019-10-25 Created: 2019-10-25 Last updated: 2019-10-25Bibliographically approved
Ugge, H., Downer, M. K., Carlsson, J., Bowden, M., Davidsson, S., Mucci, L. A., . . . Andrén, O. (2019). Circulating inflammation markers and prostate cancer. The Prostate, 79(11), 1338-1346
Open this publication in new window or tab >>Circulating inflammation markers and prostate cancer
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2019 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 11, p. 1338-1346Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Chronic inflammation is thought to influence the risk of prostate cancer. The purpose of this population-based case-control study was to evaluate the association of 48 circulating inflammation markers with prostate cancer, to identify candidate markers for further investigation.

METHODS: Serum samples collected from 235 prostate cancer patients and 198 population-based controls recruited in Örebro County, Sweden, in 1989-1991, were assessed using a multiplex bead-based immunoassay to determine concentrations of 48 circulating inflammation markers. Logistic regression was first used to evaluate the association between individual markers (highest vs lowest concentration quartile) and prostate cancer in unadjusted and mutually adjusted models. Second, patients with inflammatory conditions, metastatic or advanced prostate cancer, were excluded to address the possible influence of systemic disease on inflammation markers.

RESULTS: Individual analyses first identified 21 markers associated with prostate cancer (P < .05), which after mutual adjustment were reduced to seven markers. After the exclusion of men with conditions linked with systemic inflammation, associations between prostate cancer and deviant levels of C-X3-C motif chemokine ligand 1, platelet-derived growth factor subunit B homodimer, interleukin 10, C-C motif chemokine ligand (CCL) 21, and CCL11 remained statistically significant.

CONCLUSIONS: In this explorative study, we identified candidate inflammation markers of possible importance for prostate cancer pathophysiology, for further evaluation in prospective studies.

Place, publisher, year, edition, pages
Alan R. Liss Inc., 2019
Keywords
Circulating, cytokines, inflammation, markers, prostate cancer
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:oru:diva-74753 (URN)10.1002/pros.23842 (DOI)000473235500014 ()31212389 (PubMedID)2-s2.0-85068041866 (Scopus ID)
Note

Funding Agency:

Lions Cancerforskningsfond vid Akademiska sjukhuset i Uppsala. (Part of Lions International)

Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-08-09Bibliographically approved
Sundin, P.-O., Udumyan, R., Fall, K. & Montgomery, S. (2019). Grip strength modifies the association between estimated glomerular filtration rate and all-cause mortality [Letter to the editor]. Nephrology, Dialysis and Transplantation, 34(10), 1799-1801
Open this publication in new window or tab >>Grip strength modifies the association between estimated glomerular filtration rate and all-cause mortality
2019 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 34, no 10, p. 1799-1801Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Oxford University Press, 2019
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:oru:diva-75586 (URN)10.1093/ndt/gfz140 (DOI)000491254500024 ()31317193 (PubMedID)2-s2.0-85072904607 (Scopus ID)
Note

Funding Agencies:

Economic & Social Research Council (ESRC) RES-596-28-0001 ES/JO19119/1

Swedish county councils, Agreement on Medical Education and Research (ALF)  OLL-685971

Swedish government  OLL-685971

Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2019-11-15Bibliographically approved
Kennedy, B., Ruoqing, C., Fang, F., Valdimarsdottir, U., Montgomery, S., Larsson, H. & Fall, K. (2019). Low stress resilience in late adolescence and risk of smoking, high alcohol consumption and drug use later in life. Journal of Epidemiology and Community Health, 73(6), 469-501
Open this publication in new window or tab >>Low stress resilience in late adolescence and risk of smoking, high alcohol consumption and drug use later in life
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2019 (English)In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 73, no 6, p. 469-501Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: While compromised stress resilience constitutes a recognised risk factor for somatic and psychiatric disease development in general, the knowledge about how individual variation in vulnerability to stress may specifically influence the long-term risks of disadvantageous health behaviours is limited.

METHODS: In this Swedish cohort study, we aimed to investigate the association between stress resilience in late adolescence and adult use of addictive substances. We included 9381 men with information on psychological stress resilience measured during military conscription examinations, who later responded to an extensive health survey (mean age 34.0±7.2 years) including detailed information on substance use. We modelled continuous outcomes using linear regression, binary outcomes with logistic regression and other categorical outcomes with multinomial logistic regression.

RESULTS: We found that low stress resilience in adolescence conferred increased risks of all studied measures of addictive behaviour. After adjusting for childhood socioeconomic information, low stress resilience was associated with adult current regular smoking (relative risk ratio: 5.85, 95% CI 4.32 to 7.93), higher nicotine dependence scores (beta: 0.76, 95% CI 0.29 to 1.23), hazardous use of alcohol (>14 alcoholic drink-equivalents per week, OR: 1.72, 95% CI 1.37 to 2.16), DSM-IV criteria for alcohol dependence (OR: 1.74, 95% CI 1.35 to 2.25), and drug use (OR: 1.77, 95% CI 1.51 to 2.08). The results remained largely unchanged after further adjustments for adult educational attainment and occupation as well as for additional conscription covariates.

CONCLUSION: Low stress resilience in late adolescence appears to be associated with an increased risk of disadvantageous and addictive health behaviours in adulthood.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
Keywords
Alcohol, epidemiology, health behaviour, psychological stress, smoking
National Category
Substance Abuse
Identifiers
urn:nbn:se:oru:diva-72375 (URN)10.1136/jech-2018-211815 (DOI)000471850400004 ()30718261 (PubMedID)2-s2.0-85061156675 (Scopus ID)
Note

Funding Agencies:

European Research Council Consolidator Grant  726413 

Swedish Council for Information on Alcohol and Other Drugs  2017-0095 

Karolinska Institutet through a Senior Researcher Award  

Karolinska Institutet through a Strategic Research Area in Epidemiology Award 

Available from: 2019-02-11 Created: 2019-02-11 Last updated: 2019-11-08Bibliographically approved
Chen, R., Zhan, Y., Pedersen, N., Fall, K., Valdimarsdóttir, U. A., Hägg, S. & Fang, F. (2019). Marital status, telomere length and cardiovascular disease risk in a Swedish prospective cohort. Heart, Article ID heartjnl-2019-315629.
Open this publication in new window or tab >>Marital status, telomere length and cardiovascular disease risk in a Swedish prospective cohort
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2019 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, article id heartjnl-2019-315629Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: To investigate if marital status is associated with risk of cardiovascular disease (CVD) and to explore the potential influence of leucocyte telomere length (LTL), a marker of biological ageing, on such association.

DESIGN: Population-based prospective cohort study SETTINGS: Swedish Twin Registry.

PARTICIPANTS: Based on the Screening Across the Lifespan Twin Study from the Swedish Twin Registry, we included 10 058 twins born between 1900 and 1958 who underwent an interview between 1998 and 2002 during which information about marital status was collected. Blood samples from these participants were subsequently collected between 2004 and 2008 and used for LTL assessment using quantitative PCR technique.

MAIN OUTCOME MEASURES: Incident cases of CVD were identified through the Swedish Patient Register and Causes of Death Register through December 31, 2016. Multivariable linear regression and Cox proportional hazards regression models were used to estimate the regression coefficients (βs) and HRs with 95% CIs respectively. Potential confounders included age, sex, educational attainment and body mass index.

RESULTS: A total of 2010 participants were diagnosed with CVD during a median follow-up of 9.8 years. LTL was shorter among individuals living singly, including those who were divorced or separated (β:-0.014, 95% CI: -0.035, 0.007), widowed (β:-0.035, 95% CI: -0.061, -0.010), or living alone (β:-0.033, 95% CI: -0.052, -0.014), than individuals who were married or cohabitating. One SD increase of LTL was associated with a lower risk of CVD (HR: 0.79, 95% CI: 0.66, 0.93). Individuals who were divorced or separated, widowed, or living alone had a higher risk of CVD than individuals who were married or cohabitating. The summary HR of CVD was 1.21 (95% CI: 1.08, 1.35) when comparing individuals who were living singly, regardless of reason, with the individuals who were married or cohabitating. LTL appeared to mediate little of the association between marital status and CVD (HR additionally adjusted for LTL: 1.20; 95% CI: 1.08, 1.34).

CONCLUSIONS: Living singly, regardless of reason, was associated with a shorter LTL and a higher risk of CVD. The association between marital status and CVD was however not greatly attributable to telomere shortening.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
Keywords
Cardiac risk factors and prevention, epidemiology, quality and outcomes of care
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-77941 (URN)10.1136/heartjnl-2019-315629 (DOI)31727634 (PubMedID)
Available from: 2019-11-20 Created: 2019-11-20 Last updated: 2019-11-20Bibliographically approved
Jerlström, T., Ruoqing, C., Liedberg, F., Andrén, O., Ströck, V., Aljabery, F. A. S., . . . Fall, K. (2019). No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy: a nation-wide register-based study. World journal of urology
Open this publication in new window or tab >>No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy: a nation-wide register-based study
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2019 (English)In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726Article in journal (Refereed) Epub ahead of print
Abstract [en]

PURPOSE: Preoperative chemotherapy is underused in conjunction with radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) due to concerns for complications and delay of surgery. Prospective data on short-term complications from population-based settings with frequent use of preoperative chemotherapy and standardised reporting of complications is lacking.

METHODS: We identified 1,340 patients who underwent RC between 2011 and 2015 in Sweden due to MIBC according to the Swedish Cystectomy Register. These individuals were followed through linkages to several national registers. Propensity score adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for complications and death within 90 days of surgery, comparing patients receiving preoperative chemotherapy or not.

RESULTS: Minimum two cycles of preoperative chemotherapy were given to 519 (39%) of the patients, who on average tended to be younger, have higher education, better physical status, and more advanced bladder cancer than patients not receiving chemotherapy. After adjusting for these and other parameters, there was no association between treatment with preoperative chemotherapy and short-term complications (OR 1.06 95% CI 0.82-1.39) or mortality (OR 0.75 95% CI 0.36-1.55). We observed a risk reduction for gastrointestinal complications among patients who received preoperative chemotherapy compared with those who did not (OR 0.49 95% CI 0.30-0.81).

CONCLUSION: This nation-wide population-based observational study does not suggest that preoperative chemotherapy, in a setting with high utilisation of such treatment, is associated with an increased risk of short-term complications in MIBC patients treated with radical cystectomy.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Bladder cancer, Induction chemotherapy, Neoadjuvant chemotherapy, Postoperative complications, Radical cystectomy
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:oru:diva-73968 (URN)10.1007/s00345-019-02770-2 (DOI)31020424 (PubMedID)
Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2019-04-29Bibliographically approved
Landberg, A., Fält, A., Montgomery, S., Sundqvist, P. & Fall, K. (2019). Overweight and obesity during adolescence increases the risk of renal cell carcinoma. International Journal of Cancer, 145(5), 1232-1237
Open this publication in new window or tab >>Overweight and obesity during adolescence increases the risk of renal cell carcinoma
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, no 5, p. 1232-1237Article in journal (Refereed) Published
Abstract [en]

While overweight among adults has been linked with renal cell carcinoma (RCC) risk, little is known about the potential influence of overweight and obesity during adolescence. To ascertain if adolescent body mass index is associated with subsequent risk of RCC, we identified a cohort of 238,788 Swedish men who underwent mandatory military conscription assessment between 1969 and 1976 at a mean age of 18.5 years. At the time of conscription assessment, physical and psychological tests were performed including measurements of height and weight. Participants were followed through linkage to the Swedish Cancer Registry to identify incident diagnoses of RCC. The association between body mass index (BMI, kg/m(2)) at conscription assessment and subsequent RCC was evaluated using multivariable Cox regression. During a follow-up of up to 37 years, 266 men were diagnosed with RCC. We observed a trend for higher RCC risk with increasing BMI during adolescence, where one-unit increase in BMI conferred a 6% increased risk of RCC (95% CI 1.01-1.10). compared to normal weight men (BMI 18.5- < 25), men with overweight (BMI 25- < 30) or obesity (BMI >= 30) had hazard ratios for RCC of 1.76 (95% CI 1.16-2.67) and 2.87 (95% CI 1.26-6.25), respectively. The link between overweight/obesity and RCC appear to be already established during late adolescence. Prevention of unhealthy weight gain during childhood and adolescence may thus be a target in efforts to decrease the burden of RCC in the adult population.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
adolescence, cancer epidemiology, obesity, overweight, renal cell carcinoma
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-72780 (URN)10.1002/ijc.32147 (DOI)000474668200007 ()30790271 (PubMedID)2-s2.0-85068033223 (Scopus ID)
Note

Funding Agency:

UK Economic and Social Research Council  ES/JO19119/1  RES-596-28-0001

Available from: 2019-02-27 Created: 2019-02-27 Last updated: 2019-11-11Bibliographically approved
Hálfdánarson, Ó. Ö., Fall, K., Ogmundsdottir, M. H., Lund, S. H., Steingrímsson, E., Ogmundsdottir, H. M. & Zoega, H. (2019). Proton pump inhibitor use and risk of breast cancer, prostate cancer, and malignant melanoma: An Icelandic population-based case-control study. Pharmacoepidemiology and Drug Safety, 28(4), 471-478
Open this publication in new window or tab >>Proton pump inhibitor use and risk of breast cancer, prostate cancer, and malignant melanoma: An Icelandic population-based case-control study
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2019 (English)In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 28, no 4, p. 471-478Article in journal (Refereed) Published
Abstract [en]

Purpose: Increased expression of Vacuolar-type H+ ATPases (V-ATPases), in the plasma membrane of cancer cells has been suggested to contribute to the development of aggressive cancer phenotypes by promoting acidic tumor microenvironments. Accumulating data suggest that proton pump inhibitors (PPIs) may elicit a chemopreventive effect via V-ATPase inhibition in some cancers, but evidence is still limited. Therefore, we aimed to explore a potential preventive role of PPIs in this study.

Methods: In this population-based case-control study, we identified incident cases of breast cancer (n=1739), prostate cancer (n=1897), and malignant melanoma (n=385) in Iceland between 2005 and 2014 from the Icelandic Cancer Registry. We assessed varying levels of PPI use through record linkages to the Icelandic Medicines Registry. For each case, we selected up to 10 age-matched, sex-matched, and calendar-matched population controls using risk-set sampling. Using conditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) controlling for NSAID use.

Results: Adjusted ORs associated with ever use of PPIs were 1.03 (95% CI: 0.92-1.16) for breast cancer, 1.12 (95% CI: 1.00-1.25) for prostate cancer, and 0.84 (95% CI: 0.69-1.12) for malignant melanoma. Analyses of high use of PPIs (>= 1000 DDDs) yielded ORs of 0.97 (95% CI: 0.78-1.19), 1.20 (0.99-1.47), and 0.59 (0.40-1.13) for breast cancer, prostate cancer, and malignant melanoma, respectively. Analyses of cumulative exposure to PPIs did not support a dose-response relationship for any of the three cancer types.

Conclusions: Our findings do not support a chemopreventive effect of PPI use on breast cancer, prostate cancer, or malignant melanoma.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
breast cancer, melanoma, pharmacoepidemiology, prostate cancer, proton pump inhibitors, V-ATPase
National Category
Public Health, Global Health, Social Medicine and Epidemiology Pharmacology and Toxicology
Identifiers
urn:nbn:se:oru:diva-74544 (URN)10.1002/pds.4702 (DOI)000467999700009 ()30565786 (PubMedID)2-s2.0-85058845482 (Scopus ID)
Note

Funding Agency:

Icelandic Research Fund  152715-053

Available from: 2019-06-03 Created: 2019-06-03 Last updated: 2019-06-03Bibliographically approved
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