| 1. |
- Gavrilov, Nemanja, et al.
(författare)
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A study of ordered mesoporous carbon doped with Co and Ni as a catalyst of oxygen reduction reaction in both alkaline and acidic media
- 2018
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Ingår i: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 349, s. 511-521
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Tidskriftsartikel (refereegranskat)abstract
- The incorporation of trace amounts (< 0.2%) of Co and Ni noticeably enhanced the catalytic activity of nitrogen free ordered mesoporous carbon (OMC) towards oxygen reduction reaction (ORR). (Co,Ni)-doped OMCs were characterized by N-2-adsorption measurements, X-ray powder diffraction, field emission scanning electron microscopy and Raman spectroscopy methods, and their ORR activity was estimated by voltammetry on rotating disk electrode in acidic and alkaline media. (Co,Ni)-doped OMCs show modest activities in acidic media, while the catalytic activity in alkaline media is rather high. The measured activities are compared to the Pt-based and Pt-free ORR catalysts reported in the literature. The number of electrons consumed per O-2 in metal-doped OMCs was found to vary between 2 and 4, which is advantageous in comparison to metal-free OMC. Also, the mass activities of metal-doped OMCs were found to be up to 2.5 times higher compared to that of metal-free OMC. We suggest that the ORR activity is governed by a balance between (i) textural properties, which determine the electrochemically accessible surface of the catalyst and which are influenced by the addition of a metal precursor, and (ii) novel active sites formed upon the introduction of metals into the carbon structure. In particular, our Density Functional Theory calculations suggest that Co and Ni atoms embedded into the single vacancies of graphene can activate the O-2 molecule and contribute to the decomposition of peroxide.
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| 2. |
- Harris, Michael, et al.
(författare)
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Identifying important health system factors that influence primary care practitioners' referrals for cancer suspicion : a European cross-sectional survey.
- 2018
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 8:9, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Cancer survival and stage of disease at diagnosis and treatment vary widely across Europe. These differences may be partly due to variations in access to investigations and specialists. However, evidence to explain how different national health systems influence primary care practitioners' (PCPs') referral decisions is lacking.This study analyses health system factors potentially influencing PCPs' referral decision-making when consulting with patients who may have cancer, and how these vary between European countries.DESIGN: Based on a content-validity consensus, a list of 45 items relating to a PCP's decisions to refer patients with potential cancer symptoms for further investigation was reduced to 20 items. An online questionnaire with the 20 items was answered by PCPs on a five-point Likert scale, indicating how much each item affected their own decision-making in patients that could have cancer. An exploratory factor analysis identified the factors underlying PCPs' referral decision-making.SETTING: A primary care study; 25 participating centres in 20 European countries.PARTICIPANTS: 1830 PCPs completed the survey. The median response rate for participating centres was 20.7%.OUTCOME MEASURES: The factors derived from items related to PCPs' referral decision-making. Mean factor scores were produced for each country, allowing comparisons.RESULTS: Factor analysis identified five underlying factors: PCPs' ability to refer; degree of direct patient access to secondary care; PCPs' perceptions of being under pressure; expectations of PCPs' role; and extent to which PCPs believe that quality comes before cost in their health systems. These accounted for 47.4% of the observed variance between individual responses.CONCLUSIONS: Five healthcare system factors influencing PCPs' referral decision-making in 20 European countries were identified. The factors varied considerably between European countries. Knowledge of these factors could assist development of health service policies to produce better cancer outcomes, and inform future research to compare national cancer diagnostic pathways and outcomes.
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| 3. |
- Harris, Michael, et al.
(författare)
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Primary care practitioners' diagnostic action when the patient may have cancer : an exploratory vignette study in 20 European countries
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:10, s. 035678-035678
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Cancer survival rates vary widely between European countries, with differences in timeliness of diagnosis thought to be one key reason. There is little evidence on the way in which different healthcare systems influence primary care practitioners' (PCPs) referral decisions in patients who could have cancer.This study aimed to explore PCPs' diagnostic actions (whether or not they perform a key diagnostic test and/or refer to a specialist) in patients with symptoms that could be due to cancer and how they vary across European countries. DESIGN: A primary care survey. PCPs were given vignettes describing patients with symptoms that could indicate cancer and asked how they would manage these patients. The likelihood of taking immediate diagnostic action (a diagnostic test and/or referral) in the different participating countries was analysed. Comparisons between the likelihood of taking immediate diagnostic action and physician characteristics were calculated. SETTING: Centres in 20 European countries with widely varying cancer survival rates. PARTICIPANTS: A total of 2086 PCPs answered the survey question, with a median of 72 PCPs per country. RESULTS: PCPs' likelihood of immediate diagnostic action at the first consultation varied from 50% to 82% between countries. PCPs who were more experienced were more likely to take immediate diagnostic action than their peers. CONCLUSION: When given vignettes of patients with a low but significant possibility of cancer, more than half of PCPs across Europe would take diagnostic action, most often by ordering diagnostic tests. However, there are substantial between-country variations.
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| 4. |
- King, Sontoria D., et al.
(författare)
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Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization
- 2023
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 32:9, s. 1265-1269
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer.METHODS: Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes.RESULTS: No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88-1.22; MR-Egger OR, 0.89; 95% CI, 0.65-1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90-1.27; MR-Egger OR, 0.93; 95% CI, 0.67-1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample.CONCLUSIONS: Genetic predisposition to NAFLD is not associated with pancreatic cancer risk.IMPACT: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.
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| 5. |
- Klein, Alison P., et al.
(författare)
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Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 x 10(-8)). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PAN-DoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 x 10(-14)), rs2941471 at 8q21.11 (HNF4G, P = 6.60 x 10(-10)), rs4795218 at 17q12 (HNF1B, P = 1.32 x 10(-8)), and rs1517037 at 18q21.32 (GRP, P = 3.28 x 10(-8)). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.
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| 6. |
- Sasamoto, Naoko, et al.
(författare)
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Development and validation of circulating CA125 prediction models in postmenopausal women
- 2019
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Ingår i: Journal of Ovarian Research. - : BioMed Central (BMC). - 1757-2215. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker.Methods: We developed and validated linear and dichotomous (>= 35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses' Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. Result The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset.Conclusions: The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.
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| 7. |
- Sasamoto, Naoko, et al.
(författare)
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Predicting Circulating CA125 Levels among Healthy Premenopausal Women
- 2019
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:6, s. 1076-1085
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (>= 35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women. Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.
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| 8. |
- Walsh, Naomi, et al.
(författare)
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Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 111:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes.Methods: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided.Results: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets.Conclusion: Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
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| 9. |
- Zhong, Jun, et al.
(författare)
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A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer
- 2020
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 112:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). Results: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEPI) and 11 at six known risk loci (5p15.33: TERT, CLPTMIL, ZDHHCIIB; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTMIL, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
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