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- Andersson-Evelönn, Emma, 1983-, et al.
(författare)
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Combining epigenetic and clinicopathological variables improves specificity in prognostic prediction in clear cell renal cell carcinoma
- 2020
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metastasized clear cell renal cell carcinoma (ccRCC) is associated with a poor prognosis. Almost one-third of patients with non-metastatic tumors at diagnosis will later progress with metastatic disease. These patients need to be identified already at diagnosis, to undertake closer follow up and/or adjuvant treatment. Today, clinicopathological variables are used to risk classify patients, but molecular biomarkers are needed to improve risk classification to identify the high-risk patients which will benefit most from modern adjuvant therapies. Interestingly, DNA methylation profiling has emerged as a promising prognostic biomarker in ccRCC. This study aimed to derive a model for prediction of tumor progression after nephrectomy in non-metastatic ccRCC by combining DNA methylation profiling with clinicopathological variables.Methods: A novel cluster analysis approach (Directed Cluster Analysis) was used to identify molecular biomarkers from genome-wide methylation array data. These novel DNA methylation biomarkers, together with previously identified CpG-site biomarkers and clinicopathological variables, were used to derive predictive classifiers for tumor progression.Results: The “triple classifier” which included both novel and previously identified DNA methylation biomarkers together with clinicopathological variables predicted tumor progression more accurately than the currently used Mayo scoring system, by increasing the specificity from 50% in Mayo to 64% in our triple classifier at 85% fixed sensitivity. The cumulative incidence of progress (pCIP5yr) was 7.5% in low-risk vs 44.7% in high-risk in M0 patients classified by the triple classifier at diagnosis.Conclusions: The triple classifier panel that combines clinicopathological variables with genome-wide methylation data has the potential to improve specificity in prognosis prediction for patients with non-metastatic ccRCC.
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| 2. |
- Crilly, Julia, et al.
(författare)
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Factors predictive of hospital admission for children via emergency departments in Australia and Sweden: an observational cross-sectional study
- 2024
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Ingår i: BMC Health Services Research. - : Springer Nature. - 1472-6963. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Identifying factors predictive of hospital admission can be useful to prospectively inform bed management and patient flow strategies and decrease emergency department (ED) crowding. It is largely unknown if admission rate or factors predictive of admission vary based on the population to which the ED served (i.e., children only, or both adults and children). This study aimed to describe the profile and identify factors predictive of hospital admission for children who presented to four EDs in Australia and one ED in Sweden.Methods: A multi-site observational cross-sectional study using routinely collected data pertaining to ED presentations made by children < 18 years of age between July 1, 2011 and October 31, 2012. Univariate and multivariate analysis were undertaken to determine factors predictive of hospital admission.Results: Of the 151,647 ED presentations made during the study period, 22% resulted in hospital admission. Admission rate varied by site; the children's EDs in Australia had higher admission rates (South Australia: 26%, Queensland: 23%) than the mixed (adult and children's) EDs (South Australia: 13%, Queensland: 17%, Sweden: 18%). Factors most predictive of hospital admission for children, after controlling for triage category, included hospital type (children's only) adjusted odds ratio (aOR):2.3 (95%CI: 2.2-2.4), arrival by ambulance aOR:2.8 (95%CI: 2.7-2.9), referral from primary health aOR:1.5 (95%CI: 1.4-1.6) and presentation with a respiratory or gastrointestinal condition (aOR:2.6, 95%CI: 2.5-2.8 and aOR:1.5, 95%CI: 1.4-1.6, respectively). Predictors were similar when each site was considered separately.Conclusions: Although the characteristics of children varied by site, factors predictive of hospital admission were mostly similar. The awareness of these factors predicting the need for hospital admission can support the development of clinical pathways.
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| 3. |
- Källberg, David, 1982-, et al.
(författare)
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Comparison of Methods for Feature Selection in Clustering of High-Dimensional RNA-Sequencing Data to Identify Cancer Subtypes
- 2021
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Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Cancer subtype identification is important to facilitate cancer diagnosis and select effective treatments. Clustering of cancer patients based on high-dimensional RNA-sequencing data can be used to detect novel subtypes, but only a subset of the features (e.g., genes) contains information related to the cancer subtype. Therefore, it is reasonable to assume that the clustering should be based on a set of carefully selected features rather than all features. Several feature selection methods have been proposed, but how and when to use these methods are still poorly understood. Thirteen feature selection methods were evaluated on four human cancer data sets, all with known subtypes (gold standards), which were only used for evaluation. The methods were characterized by considering mean expression and standard deviation (SD) of the selected genes, the overlap with other methods and their clustering performance, obtained comparing the clustering result with the gold standard using the adjusted Rand index (ARI). The results were compared to a supervised approach as a positive control and two negative controls in which either a random selection of genes or all genes were included. For all data sets, the best feature selection approach outperformed the negative control and for two data sets the gain was substantial with ARI increasing from (−0.01, 0.39) to (0.66, 0.72), respectively. No feature selection method completely outperformed the others but using the dip-rest statistic to select 1000 genes was overall a good choice. The commonly used approach, where genes with the highest SDs are selected, did not perform well in our study.
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| 4. |
- Källberg, David, 1982-, et al.
(författare)
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Large sample properties of entropy balancing estimators of average causal effects
- 2023
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Ingår i: Econometrics and Statistics. - : Elsevier. - 2452-3062.
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Tidskriftsartikel (refereegranskat)abstract
- Weighting methods are used in observational studies to adjust for covariate imbalances between treatment and control groups. Entropy balancing (EB) is an alternative to inverse probability weighting with an estimated propensity score. The EB weights are constructed to satisfy balance constraints and optimized towards stability. Large sample properties of EB estimators of the average causal treatment effect, based on the Kullback-Leibler and quadratic Rényi relative entropies, are described. Additionally, estimators of their asymptotic variances are proposed. Even though the objective of EB is to reduce model dependence, the estimators are generally not consistent unless implicit parametric assumptions for the propensity score or conditional outcomes are met. The finite sample properties of the estimators are investigated through a simulation study. The average causal effect of smoking on blood lead levels is estimated using data from the National Health and Nutrition Examination Survey.
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