1073 results found
Abelson S, Collord G, Ng SWK, et al., 2018, Prediction of acute myeloid leukaemia risk in healthy individuals, NATURE, Vol: 559, Pages: 400-+, ISSN: 0028-0836
Agudo A, Cayssials V, Bonet C, et al., 2018, Inflammatory potential of the diet and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 107, Pages: 607-616, ISSN: 0002-9165
Andersen V, Chan S, Luben R, et al., 2018, Fibre intake and the development of inflammatory bowel disease: A European prospective multi-centre cohort study (EPIC-IBD), JOURNAL OF CROHNS & COLITIS, Vol: 12, Pages: 129-136, ISSN: 1873-9946
Assi N, Gunter MJ, Thomas DC, et al., 2018, Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 108, Pages: 117-126, ISSN: 0002-9165
Assi N, Thomas DC, Leitzmann M, et al., 2018, Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case-Control Study in EPIC, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 27, Pages: 531-540, ISSN: 1055-9965
Aune D, Feng T, Schlesinger S, et al., 2018, Diabetes mellitus, blood glucose and the risk of atrial fibrillation: A systematic review and meta-analysis of cohort studies, JOURNAL OF DIABETES AND ITS COMPLICATIONS, Vol: 32, Pages: 501-511, ISSN: 1056-8727
Aune D, Mahamat-Saleh Y, Norat T, et al., 2018, Body fatness, diabetes, physical activity and risk of kidney stones: a systematic review and meta-analysis of cohort studies., Eur J Epidemiol
We conducted a systematic review and meta-analysis to clarify the association between adiposity, diabetes, and physical activity and the risk of kidney stones. PubMed and Embase were searched up to April 22nd 2018 for relevant studies. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects models. Thirteen cohort studies were included. The summary relative risk was 1.21 (95% CI 1.12-1.30, I2 = 76%, n = 8) per 5 unit increment in BMI, 1.16 (95% CI 1.12-1.19, I2 = 0%, n = 5) per 10 cm increase in waist circumference, 1.06 (95% CI 1.04-1.08, I2 = 67%, n = 3) per 5 kg increase in weight and 1.12 (95% CI 1.06-1.18, I2 = 86%, n = 3) per 5 kg of weight gain. The summary RR was 1.16 (95% CI 1.03-1.31, I2 = 51%, n = 10) for participants with diabetes compared to participants without diabetes, and 0.93 (95% CI 0.78-1.10, I2 = 80%, n = 4) for high vs. low physical activity. These results suggest a positive association between adiposity and diabetes and the risk of kidney stones, but no association with physical activity.
Aune D, Schlesinger S, Norat T, et al., 2018, Tobacco smoking and the risk of sudden cardiac death: a systematic review and meta-analysis of prospective studies, EUROPEAN JOURNAL OF EPIDEMIOLOGY, Vol: 33, Pages: 509-521, ISSN: 0393-2990
Aune D, Schlesinger S, Norat T, et al., 2018, Body mass index, abdominal fatness, and the risk of sudden cardiac death: a systematic review and dose-response meta-analysis of prospective studies, EUROPEAN JOURNAL OF EPIDEMIOLOGY, Vol: 33, Pages: 711-722, ISSN: 0393-2990
Aune D, Schlesinger S, Norat T, et al., 2018, Diabetes mellitus and the risk of sudden cardiac death: A systematic review and meta-analysis of prospective studies, NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES, Vol: 28, Pages: 543-556, ISSN: 0939-4753
Aune D, Schlesinger S, Norat T, et al., 2018, Tobacco smoking and the risk of atrial fibrillation: A systematic review and meta-analysis of prospective studies., Eur J Prev Cardiol
Background Epidemiological studies on smoking and atrial fibrillation have been inconsistent, with some studies showing a positive association while others have found no association. It is also unclear whether there is a dose-response relationship between the number of cigarettes smoked or pack-years and the risk of atrial fibrillation. We conducted a systematic review and meta-analysis to clarify the association. Design Systematic review and meta-analysis. Methods We searched the PubMed and Embase databases for studies of smoking and atrial fibrillation up to 20 July 2017. Prospective studies and nested case-control studies within cohort studies reporting adjusted relative risk estimates and 95% confidence intervals (CIs) of atrial fibrillation associated with smoking were included. Summary relative risks (95% CIs) were estimated using a random effects model. Results Twenty nine prospective studies (22 publications) were included. The summary relative risk was 1.32 (95% CI 1.12-1.56, I2 = 84%, n = 11 studies) for current smokers, 1.09 (95% CI 1.00-1.18, I2 = 33%, n = 9) for former smokers and 1.21 (95% CI 1.12-1.31, I2 = 80%, n = 14) for ever smokers compared to never smokers. Comparing current versus non-current smokers the summary relative risk was 1.33 (95% CI 1.14-1.56, I2 = 78%, n = 10). The summary relative risk was 1.14 (95% CI 1.10-1.20, I2 = 0%, n = 3) per 10 cigarettes per day and 1.16 (95% CI 1.09-1.25, I2 = 49%, n = 2) per 10 pack-years and there was no evidence of a non-linear association for cigarettes per day, Pnon-linearity = 0.17. Conclusions The current meta-analysis suggests that smoking is associated with an increased risk of atrial fibrillation in a dose-dependent matter, but the association is weaker among former smokers compared to current smokers.
Aune D, Snekvik I, Schlesinger S, et al., 2018, Body mass index, abdominal fatness, weight gain and the risk of psoriasis: a systematic review and dose-response meta-analysis of prospective studies., Eur J Epidemiol
Greater body mass index (BMI) has been associated with increased risk of psoriasis in case-control and cross-sectional studies, however, the evidence from prospective studies has been limited. We conducted a systematic review and dose-response meta-analysis of different adiposity measures and the risk of psoriasis to provide a more robust summary of the evidence based on data from prospective studies. PubMed and Embase databases were searched for relevant studies up to August 8th 2017. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random effects model. The summary relative risk (RR) for a 5 unit increment in BMI was 1.19 (95% CI 1.10-1.28, I2 = 83%, n = 7). The association appeared to be stronger at higher compared to lower levels of BMI, pnonlinearity < 0.0001, and the lowest risk was observed at a BMI around 20. The summary RR was 1.24 (95% CI 1.17-1.31, I2 = 0%, pheterogeneity = 0.72, n = 3) per 10 cm increase in waist circumference, 1.37 (95% CI 1.23-1.53, I2 = 0%, pheterogeneity = 0.93, n = 3) per 0.1 unit increase in waist-to-hip ratio, and 1.11 (95% CI 1.07-1.16, I2 = 47%, pheterogeneity = 0.15, n = 3) per 5 kg of weight gain. Adiposity as measured by BMI, waist circumference, waist-to-hip ratio, and weight gain is associated with increased risk of psoriasis.
Butt J, Jenab M, Willhauck-Fleckenstein M, et al., 2018, Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer, INTERNATIONAL JOURNAL OF CANCER, Vol: 143, Pages: 245-252, ISSN: 0020-7136
Cairat M, Fournier A, Murphy N, et al., 2018, Nonsteroidal anti-inflammatory drug use and breast cancer risk in a European prospective cohort study., Int J Cancer
Experimental studies have shown a protective effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer development. However, results from epidemiological cohort studies are less consistent. Our objective was to assess the association between NSAID use and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Self-reported information on NSAID use at baseline has been collected in five EPIC countries. Multivariable Cox regression models were used to estimate hazard ratios for the association of NSAID use with breast cancer incidence with adjustment for potential confounders. We also assessed effect modification by breast cancer risk factors and examined the associations within specific breast cancer subtypes. Among the 140,981 women included in the analysis, 7% were regularly using NSAIDs at baseline. During a median follow-up time period of 13 years, 7,379 incident breast cancer cases were diagnosed (816 in situ and 6,563 invasive). There were no statistically significant associations between NSAID use and breast cancer risk, overall and by subtypes. However, a statistically significant interaction was observed for invasive cases between NSAID use and ever use of menopausal hormonal therapy (MHT) among postmenopausal women [MHT users: HRNSAID use = 0.84 (0.73-0.96); non MHT users: HRNSAID use = 1.08 (0.93-1.25); pinteraction = 0.05]. Our results indicate potential effect modification of MHT use on the association between use of NSAIDs and breast cancer risk which deserves in-depth investigation in studies with accurate data on both NSAID and MHT use.
Campanella G, Gunter MJ, Polidoro S, et al., 2018, Epigenome-wide association study of adiposity and future risk of obesity-related diseases., Int J Obes (Lond)
BACKGROUND: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction. METHODS: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population. RESULTS: We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10-8 to 3.27×10-18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10-7), higher triglyceride levels (P = 5.37×10-9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10-10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P < 1.6×10-3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarcti
Dadaev T, Saunders EJ, Newcombe PJ, et al., 2018, Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723
Dossus L, Franceschi S, Biessy C, et al., 2018, Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study, INTERNATIONAL JOURNAL OF CANCER, Vol: 142, Pages: 1332-1342, ISSN: 0020-7136
Fortner RT, Schock H, Le Cornet C, et al., 2018, Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels: Results from the EPIC cohort, INTERNATIONAL JOURNAL OF CANCER, Vol: 142, Pages: 1355-1360, ISSN: 0020-7136
Gunter MJ, Murphy N, Muller DC, et al., 2018, Coffee Drinking and Mortality in 10 European Countries Response, ANNALS OF INTERNAL MEDICINE, Vol: 168, Pages: 380-381, ISSN: 0003-4819
Integrative Analysis of Lung Cancer Etiology and Risk INTEGRAL Consortium for Early Detection of Lung Cancer, Guida F, Sun N, et al., 2018, Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins., JAMA Oncol
Importance: There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases. Objective: To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria. Design, Setting, and Participants: Prediagnostic samples from 108 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and samples from 216 smoking-matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were used to develop a biomarker risk score based on 4 proteins (cancer antigen 125 [CA125], carcinoembryonic antigen [CEA], cytokeratin-19 fragment [CYFRA 21-1], and the precursor form of surfactant protein B [Pro-SFTPB]). The biomarker score was subsequently validated blindly using absolute risk estimates among 63 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and 90 matched controls from 2 large European population-based cohorts, the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS). Main Outcomes and Measures: Model validity in discriminating between future lung cancer cases and controls. Discrimination estimates were weighted to reflect the background populations of EPIC and NSHDS validation studies (area under the receiver-operating characteristics curve [AUC], sensitivity, and specificity). Results: In the validation study of 63 ever-smoking patients with lung cancer and 90 matched controls (mean [SD] age, 57.7 [8.7] years; 68.6% men) from EPIC and NSHDS, an integrated risk prediction model that combined smoking exposure with the biomarker score yielded an AUC of 0.83 (95% CI, 0.76-0.90) compared with 0.73 (95% CI, 0.64-0.82) for a model based on smoking exposure alone (P = .003 for difference in AUC). At an overall specificity
Kaaks R, Fortner RT, Huesing A, et al., 2018, Tumor-associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation, INTERNATIONAL JOURNAL OF CANCER, Vol: 143, Pages: 515-526, ISSN: 0020-7136
Kröger J, Meidtner K, Stefan N, et al., 2018, Circulating Fetuin-A and risk of Type 2 Diabetes: a Mendelian randomization analysis, Diabetes, Vol: 67, Pages: 1200-1205, ISSN: 0012-1797
Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. We aimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian Randomization study with SNPs located in the fetuin-A-encodingAHSGgene. We used data from eight European countries of the prospective EPIC-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 cases. A genetic score of theAHSGSNPs was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 µg/ml higher fetuin-A concentration with diabetes risk (HR 1.02 [95%-CI 0.97, 1.07]). Combining our results with those from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 cases) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistical evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study doesn't support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.
Landais E, Moskal A, Mullee A, et al., 2018, Coffee and Tea Consumption and the Contribution of Their Added Ingredients to Total Energy and Nutrient Intakes in 10 European Countries: Benchmark Data from the Late 1990s, NUTRIENTS, Vol: 10, ISSN: 2072-6643
Li SX, Imamura F, Schulze MB, et al., 2018, Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries, DIABETOLOGIA, Vol: 61, Pages: 1325-1332, ISSN: 0012-186X
Lin C, Travis RC, Appleby PN, et al., 2018, Pre-diagnostic circulating insulin-like growth factor-I and bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition., Int J Cancer
Previous in vitro and case-control studies have found an association between the insulin-like growth factor (IGF)-axis and bladder cancer risk. Circulating concentrations of IGF-I have also been found to be associated with an increased risk of several cancer types; however, the relationship between pre-diagnostic circulating IGF-I concentrations and bladder cancer has never been studied prospectively. We investigated the association of pre-diagnostic plasma concentrations of IGF-I with risk of overall bladder cancer and urothelial cell carcinoma (UCC) in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 843 men and women diagnosed with bladder cancer between 1992 and 2005 were matched with 843 controls by recruitment centre, sex, age at recruitment, date of blood collection, duration of follow-up, time of day and fasting status at blood collection using an incidence density sampling protocol. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for smoking status. No association was found between pre-diagnostic circulating IGF-I concentration and overall bladder cancer risk (adjusted OR for highest versus lowest fourth: 0.91, 95% CI: 0.66-1.24, Ptrend =0.40) or UCC (n of cases=776; 0.91, 0.65-1.26, Ptrend =0.40). There was no significant evidence of heterogeneity in the association of IGF-I with bladder cancer risk by tumour aggressiveness, sex, smoking status, or by time between blood collection and diagnosis (Pheterogeneity >0.05 for all). This first prospective study indicates no evidence of an association between plasma IGF-I concentrations and bladder cancer risk. This article is protected by copyright. All rights reserved.
McCullough ML, Zoltick ES, Weinstein SJ, et al., 2018, Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts., J Natl Cancer Inst
Background: Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. Methods: We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. Results: Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection. Conclusions: Higher circula
Meidtner K, Podmore C, Kroger J, et al., 2018, Interaction of Dietary and Genetic Factors Influencing Body Iron Status and Risk of Type 2 Diabetes Within the EPIC-InterAct Study, DIABETES CARE, Vol: 41, Pages: 277-285, ISSN: 0149-5992
Murphy N, Ward HA, Jenab M, et al., 2018, Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study., Clin Gastroenterol Hepatol
BACKGROUND AND AIMS: Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most have been of insufficient size to identify heterogeneous associations with precision. METHODS: In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumors at different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests. RESULTS: After 14.9 years (median) follow-up of 521,330 men and women, 6,291 colorectal cancer cases occurred. Physical activity was inversely related to proximal colon and distal colon cancer, but not to rectal cancer (P-heterogeneity=0.03). Height was positively associated with proximal and distal colon cancer only, but not rectal cancer (P-heterogeneity=0.0001). For men, but not women, heterogeneous relationships were observed for body mass index (P-heterogeneity=0.008) and waist circumference (P-heterogeneity=0.03), with weaker positive associations found for rectal cancer, compared to proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P-heterogeneity=0.05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors. CONCLUSIONS: The physical activity, anthropometry, and smoking relationships with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.
Naudin S, Li K, Jaouen T, et al., 2018, Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study, INTERNATIONAL JOURNAL OF CANCER, Vol: 143, Pages: 801-812, ISSN: 0020-7136
Premenopausal Breast Cancer Collaborative Group, Schoemaker MJ, Nichols HB, et al., 2018, Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women., JAMA Oncol
Importance: The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. Objective: To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. Design, Setting, and Participants: This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017. Exposures: Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years. Main Outcomes and Measures: Invasive or in situ premenopausal breast cancer. Results: Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs <17.
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