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| 4. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 11. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 12. |
- Kang, E. Y., et al.
(författare)
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CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study
- 2023
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 129:5, s. 697-713
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. Methods: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. Results: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. Conclusion: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
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| 14. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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- Mueller, Stefanie H., et al.
(författare)
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Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
- 2023
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Ingår i: Genome Medicine. - : BioMed Central (BMC). - 1756-994X. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
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| 22. |
- Meagher, N. S., et al.
(författare)
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A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases
- 2019
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 32, s. 1834-1846
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Tidskriftsartikel (refereegranskat)abstract
- Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7−/CK20+/CDX2+/PAX8−. This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1–50% of tumor cells) and diffuse (>50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker indistinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice. © 2019, The Author(s), under exclusive licensc to United States & Canadian Academy of Pathology.
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| 24. |
- Zanti, Maria, et al.
(författare)
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A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2
- 2023
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 2023
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Tidskriftsartikel (refereegranskat)abstract
- A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
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| 27. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 29. |
- Strand, Tor A, et al.
(författare)
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Folate, but not vitamin B-12 status, predicts respiratory morbidity in north Indian children.
- 2007
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Ingår i: American Journal of Clinical Nutrition. - 0002-9165 .- 1938-3207. ; 86:1, s. 139-144
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Vitamin deficiencies are often part of malnutrition, which predisposes to acute lower respiratory tract infections. OBJECTIVE: The objective was to measure the association between cobalamin and folate status and subsequent respiratory morbidity. DESIGN: A prospective cohort study was conducted in 2482 children aged 6-30 mo nested in a zinc supplementation trial. We measured plasma concentrations of folate, cobalamin, methylmalonic acid, and total homocysteine (tHcy) and followed the children for 4 mo. RESULTS: We observed 1176 episodes of acute lower respiratory tract infections. Children with folate concentrations in the lowest quartile (interquartile range: 6.4-20.0 nmol/L) had a 44% higher incidence [adjusted incidence rate ratio (IRR): 1.44; 95% CI: 1.23, 1.70] of acute lower respiratory tract infections than did children in the other 3 quartiles. For tHcy, the IRR was 1.24 (1.07, 1.40) in a comparison of those in the highest quartile with those in the other quartiles. Breastfeeding was associated with high folate concentrations and protection against subsequent respiratory tract infections. This protection was significantly and substantially reduced after adjustment for plasma folate concentrations at baseline. Compared with the children in the other 3 quartiles, the IRR for being in the lowest quartile of cobalamin was 1.13 (0.76, 1.03) and for being in the highest quartile of methylmalonic acid was 1.12 (0.96, 1.31). CONCLUSIONS: Poor folate status appears to be an independent risk factor for lower respiratory tract infections in young children. This study also suggests that the protective effect of breastfeeding is partly mediated by folate provided through breast milk.
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| 30. |
- Chude-Okonkwo, Uche A. K., et al.
(författare)
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Exploring the Impact of Ligand Residence Time on Molecular Communication System Performance
- 2019
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Ingår i: 2019 IEEE Global Communications Conference (GLOBECOM). - : IEEE.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Information reception in artificially synthesized molecular communication (MC) systems ideally follows the mechanisms employed by natural nanosystems to communicate. One of such reception mechanism is the so called ligand-receptor binding. Contemporary research in MC has considerably discussed this mechanism; however, the impact of a crucial parameter associated with the ligand-receptor binding action has not been given appropriate attention in the MC literature. This parameter is termed the residence time, and has played very crucial role in defining for instance, the efficacy of drugs in therapeutic processes; hence, it is critical in the performance of MC. In this paper, we employ biophysical approach to model and discuss the influence of the ligand residence time on the performance of MC systems. The performance metrics considered here are the receiver sensitivity and the intersymbol interference. Numerical results that expose the impact of the residence time on these metrics, and the interrelationships between these metrics in MC system, are discussed.
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| 31. |
- Chude-Okonkwo, Uche A. K., et al.
(författare)
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Information-Theoretic Model and Analysis of Molecular Signaling in Targeted Drug Delivery
- 2020
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Ingår i: IEEE Transactions on Nanobioscience. - : IEEE. - 1536-1241 .- 1558-2639. ; 19:2, s. 270-284
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Tidskriftsartikel (refereegranskat)abstract
- Targeted drug delivery (TDD) modality promises a smart localization of appropriate dose of therapeutic drugs to the targeted part of the body at reduced system toxicity. To achieve the desired goals of TDD, accurate analysis of the system is important. Recent advances in molecular communication (MC) present prospects to analyzing the TDD process using engineering concepts and tools. Specifically, the MC platform supports the abstraction of TDD process as a communication engineering problem in which the injection and transportation of drug particles in the human body and the delivery to a specific tissue or organ can be analyzed using communication engineering tools. In this paper we stand on the MC platform to present the information-theoretic model and analysis of the TDD systems. We present a modular structure of the TDD system and the probabilistic models of the MC-abstracted modules in an intuitive manner. Simulated results of information-theoretic measures such as the mutual information are employed to analyze the performance of the TDD system. Results indicate that uncertainties in drug injection/release systems, nanoparticles propagation channel and nanoreceiver systems influence the mutual information of the system, which is relative to the system’s bioequivalence measure.
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| 32. |
- Chude-Okonkwo, Uche A.K., et al.
(författare)
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Molecular Communication and Nanonetwork for Targeted Drug Delivery : a survey
- 2017
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Ingår i: IEEE Communications Surveys and Tutorials. - : Institute of Electrical and Electronics Engineers (IEEE). - 1553-877X. ; 19:4, s. 3046-3096
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Tidskriftsartikel (refereegranskat)abstract
- Molecular communication (MC) and molecular network (MN) are communication paradigms that use biochemical signalling to achieve information exchange among naturally and artificially synthesized nanosystems. Among the envisaged application areas of MC and MN is the field of nanomedicine where the subject of targeted drug delivery (TDD) is at the forefront. Typically, when someone gets sick, therapeutic drugs are administered to the person for healing purpose. Since no therapeutic drug can be effective until it is delivered to the target site in the body, different modalities to improve the delivery of drugs to the targeted sites are being explored in contemporary research. The most promising of these modalities is TDD. TDD modality promises a smart localization of appropriate dose of therapeutic drugs to the targeted part of the body at reduced system toxicity. Research in TDD has been going on for many years in the field of medical science; however, the translation of expectations and promises to clinical reality has not been satisfactorily achieved because of several challenges. The exploration of TDD ideas under the MC and MN paradigms is considered as an option to addressing these challenges and to facilitate the translation of TDD from the bench to the patients’ bedsides. Over the past decade, there have been some research efforts made in exploring the ideas of TDD on the MC and MN platforms. While the number of research output in terms of scientific articles is few at the moment, the desire in the scientific community to participate in realizing the goal of TDD is quite high as is evidence from the rise in research output over the last few years. To increase awareness and provide the multidisciplinary research community with the necessary background information on TDD, this paper presents a visionary survey of this subject within the domain of MC and MN. We start by introducing in an elaborate manner, the motivation behind the application of MC and MN paradigms to the study and implementation of TDD. Specifically, an explanation on how MC-based TDD concepts differ from traditional TDD being explored under the field of medical science is provided. We also summarize the taxonomy of the different perspectives through which MC-based TDD research can be viewed. System models and design challenges/requirements for developing MC-based TDD are discussed. Various metrics that can be used to evaluate the performance of MC-based TDD systems are highlighted. We also provide a discussion on the envisaged path from contemporary research activities to clinical implementation of the MC-based TDD. Finally, we discuss issues such as informatics and software tools, as well as issues that border on the requirement for standards and regulatory policies in MC-based TDD research and practice.
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| 33. |
- Chude-Okonkwo, U.A.K., et al.
(författare)
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Simulation analysis of inter-symbol interference in diffusion-based molecular communication with non-absorbing receiver
- 2017
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Ingår i: Proceedings of the 4th ACM International Conference on Nanoscale Computing and Communication, NanoCom 2017. - New York : ACM Digital Library.
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Konferensbidrag (refereegranskat)abstract
- This paper presents the analysis of inter-symbol interference (ISI) in a typical diffusion-based molecular communication system for a non-absorbing molecular receiver with no consideration to any artificially applied ISI mitigation technique. We employ stochastic simulation approach to analyze the influence of varied number of transmitted molecules, and molecules' degradation rates.
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| 34. |
- Heinze, Karolin, et al.
(författare)
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Validated biomarker assays confirm ARID1A loss is confounded with MMR deficiency, CD8 TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas.
- 2021
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Ingår i: The Journal of pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 256:4, s. 388-401
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Tidskriftsartikel (refereegranskat)abstract
- ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1,623 endometriosis-associated ovarian carcinomas, including 1,078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p=0.012), and associated with MMRd (p<0.001), and presence of CD8+ TIL (p=0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOC we also observed an association between ARID1A loss-of-function mutation as a result of small indels (p=0.035, versus single nucleotide variants). In ENOC, the association between ARID1A loss, CD8+ TIL, and age, appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8+ TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss-of-function mutations in endometriosis-associated ovarian cancers and brings clarity to the prognostic significance. This article is protected by copyright. All rights reserved.
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| 35. |
- Kobel, M., et al.
(författare)
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p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
- 2023
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Ingår i: Journal of Pathology Clinical Research. - : Wiley. - 2056-4538. ; 9:3, s. 208-222
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
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| 36. |
- Koen, Etienne, et al.
(författare)
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A particle-in-cell approach to obliquely propagating electrostatic waves
- 2014
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Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 21:9
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Tidskriftsartikel (refereegranskat)abstract
- The electron-acoustic and beam-driven modes associated with electron beams have previouslybeen identified and studied numerically. These modes are associated with Broadband ElectrostaticNoise found in the Earth’s auroral and polar cusp regions. Using a 1-D spatial Particle-in-Cell sim-ulation, the electron-acoustic instability is studied for a magnetized plasma, which includes coolions, cool electrons and a hot, drifting electron beam. Both the weakly and strongly magnetizedregimes with varying wave propagation angle, h, with respect to the magnetic field are studied. Theamplitude and frequency of the electron-acoustic mode are found to decrease with increasing h.The amplitude of the electron-acoustic mode is found to significantly grow at intermediate wave-number ranges. It reaches a saturation level at the point, where a plateau forms in the hot electron velocity distribution after which the amplitude of the electron-acoustic mode decays
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| 37. |
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| 39. |
- Koen, Etienne, et al.
(författare)
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Extracting growth rates from a Particle-In-Cell simulation
- 2012
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Ingår i: PROCEEDINGS OF SAIP2012. - : SOUTH AFRICAN INST PHYSICS. ; , s. 400-404
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Konferensbidrag (refereegranskat)abstract
- Using a Particle-In-Cell simulation, the characteristics of electrostatic waves are investigated in a plasma containing 3 electron components (hot, cold and beam electrons) and a cold ion population. Three electrostatic modes are excited, namely electron plasma, electron acoustic and beam driven waves. These modes have a broad frequency spectrum and have been associated with intense broadband electrostatic noise observed in the Earth's auroral zone. The growth rates of the beam mode is studied by constructing a growth rate curve from the electric field data. The beam mode is found to have a high growth rate for an intermediate range of wave numbers while it is damped elsewhere.
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| 40. |
- Koen, Etienne J., et al.
(författare)
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A simulation approach of high-frequency electrostatic waves found in Saturn's magnetosphere
- 2012
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Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 19:4, s. 042102-
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Tidskriftsartikel (refereegranskat)abstract
- Using a particle-in-cell simulation, the characteristics of electron plasma and electron acoustic waves are investigated in plasmas containing an ion and two electron components. The electron velocities are modeled by a combination of two kappa distributions. The model applies to the extended plasma sheet region in Saturn's magnetosphere where the cool and hot electron velocities are found to have low indices, kappa(c) similar or equal to 2 and kappa(h) similar or equal to 4. For such low values of kappa(c) and kappa(h), the electron plasma and electron acoustic waves are coupled. The model predicts weakly damped electron plasma waves while electron acoustic waves should also be observable, although less prominent.
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| 41. |
- Koen, Etienne J., et al.
(författare)
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One-dimensional Particle-In-Cell simulation of electron beam plasma interaction
- 2011
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Ingår i: URSI Gen. Assem. Sci. Symp., URSIGASS. - 9781424451173 ; , s. 6051147-
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Konferensbidrag (refereegranskat)abstract
- The theory of the two-stream instability is used to validate the initial phase of a developing code which ultimately aims to simulate the generation of VLF chorus. A one dimensional Particle-in-Cell simulation shows that waves are generated when a warm electron beam is injected into a cold background plasma with components of the electric field being excited. After a few time steps the phase space reveals a distortion of the beam and the creation of potential holes, causing electrons to oscillate.
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| 42. |
- Koen, Etienne, et al.
(författare)
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Particle-in-cell simulations of beam-driven electrostatic waves in a plasma
- 2012
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Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 19:4, s. 042101-
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Tidskriftsartikel (refereegranskat)abstract
- Using a particle-in-cell simulation, the characteristics of electrostatic waves are investigated in a three-electron component plasma including an electron beam. A Maxwellian distribution is used to describe the electron velocities. Three electrostatic modes are excited, namely electron plasma, electron acoustic, and beam-driven waves. These modes have a broad frequency spectrum and have been associated with intense broadband electrostatic noise observed in the Earth's auroral zone. The simulation results compare well with analytical dispersion and growth rate relations. This agreement serves to validate the simulation technique.
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| 43. |
- Koen, Etienne, et al.
(författare)
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Particle-in-cell simulations of ion-acoustic waves with application to Saturn's magnetosphere
- 2014
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Ingår i: Physics of Plasmas. - : American Institute of Physics (AIP). - 1070-664X .- 1089-7674. ; 21:072122
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Tidskriftsartikel (refereegranskat)abstract
- Using a particle-in-cell simulation, the dispersion and growth rate of the ion-acoustic mode areinvestigated for a plasma containing two ion and two electron components. The electron velocitiesare modelled by a combination of two kappa distributions, as found in Saturn’s magnetosphere.The ion components consist of adiabatic ions and an ultra-low density ion beam to drive a veryweak instability, thereby ensuring observable waves. The ion-acoustic mode is explored for a rangeof parameter values such as j, temperature ratio, and density ratio of the two electron components.The phase speed, frequency range, and growth rate of the mode are investigated. Simulations ofdouble-kappa two-temperature plasmas typical of the three regions of Saturn’s magnetosphere are also presented and analysed.
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| 44. |
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| 45. |
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