Imputation of missing values of tumour stage in population-based cancer registration

<p>Abstract</p> <p>Background</p> <p>Missing data on tumour stage information is a common problem in population-based cancer registries. Statistical analyses on the level of tumour stage may be biased, if no adequate method for handling of missing data is applied. In order to determine a useful way to treat missing data on tumour stage, we examined different imputation models for multiple imputation with chained equations for analysing the stage-specific numbers of cases of malignant melanoma and female breast cancer.</p> <p>Methods</p> <p>This analysis was based on the malignant melanoma data set and the female breast cancer data set of the cancer registry Schleswig-Holstein, Germany. The cases with complete tumour stage information were extracted and their stage information partly removed according to a MAR missingness-pattern, resulting in five simulated data sets for each cancer entity. The missing tumour stage values were then treated with multiple imputation with chained equations, using polytomous regression, predictive mean matching, random forests and proportional sampling as imputation models. The estimated tumour stages, stage-specific numbers of cases and survival curves after multiple imputation were compared to the observed ones.</p> <p>Results</p> <p>The amount of missing values for malignant melanoma was too high to estimate a reasonable number of cases for each UICC stage. However, multiple imputation of missing stage values led to stage-specific numbers of cases of T-stage for malignant melanoma as well as T- and UICC-stage for breast cancer close to the observed numbers of cases. The observed tumour stages on the individual level, the stage-specific numbers of cases and the observed survival curves were best met with polytomous regression or predictive mean matching but not with random forest or proportional sampling as imputation models.</p> <p>Conclusions</p> <p>This limited simulation study indicates that multiple imputation with chained equations is an appropriate technique for dealing with missing information on tumour stage in population-based cancer registries, if the amount of unstaged cases is on a reasonable level.</p

Deguelin Attenuates Reperfusion Injury and Improves Outcome after Orthotopic Lung Transplantation in the Rat

The main goal of adequate organ preservation is to avoid further cellular metabolism during the phase of ischemia. However, modern preservation solutions do rarely achieve this target. In donor organs hypoxia and ischemia induce a broad spectrum of pathologic molecular mechanisms favoring primary graft dysfunction (PGD) after transplantation. Increased hypoxia-induced transcriptional activity leads to increased vascular permeability which in turn is the soil of a reperfusion edema and the enhancement of a pro-inflammatory response in the graft after reperfusion. We hypothesize that inhibition of the respiration chain in mitochondria and thus inhibition of the hypoxia induced mechanisms might reduce reperfusion edema and consecutively improve survival in vivo. In this study we demonstrate that the rotenoid Deguelin reduces the expression of hypoxia induced target genes, and especially VEGF-A, dose-dependently in hypoxic human lung derived cells. Furthermore, Deguelin significantly suppresses the mRNA expression of the HIF target genes VEGF-A, the pro-inflammatory CXCR4 and ICAM-1 in ischemic lungs vs. control lungs. After lung transplantation, the VEGF-A induced reperfusion-edema is significantly lower in Deguelin-treated animals than in controls. Deguelin-treated rats exhibit a significantly increased survival-rate after transplantation. Additionally, a downregulation of the pro-inflammatory molecules ICAM-1 and CXCR4 and an increase in the recruitment of immunomodulatory monocytes (CD163+ and CD68+) to the transplanted organ involving the IL4 pathway was observed. Therefore, we conclude that ischemic periods preceding reperfusion are mainly responsible for the increased vascular permeability via upregulation of VEGF. Together with this, the resulting endothelial dysfunction also enhances inflammation and consequently lung dysfunction. Deguelin significantly decreases a VEGF-A induced reperfusion edema, induces the recruitment of immunomodulatory monocytes and thus improves organ function and survival after lung transplantation by interfering with hypoxia induced signaling

Classifying the evolutionary and ecological features of neoplasms

The consensus conference was supported by Wellcome Genome Campus Advanced Courses and Scientific Conferences. C.C.M. is supported in part by US NIH grants P01 CA91955, R01 CA149566, R01 CA170595, R01 CA185138 and R01 CA140657 as well as CDMRP Breast Cancer Research Program Award BC132057. M.J. is supported by NIH grant K99CA201606. K.S.A. is supported by NCI 5R21 CA196460. K. Polyak is supported by R35 CA197623, U01 CA195469, U54 CA193461, and the Breast Cancer Research Foundation. K.J.P. is supported by NIH grants CA143803, CA163124, CA093900 and CA143055. D.P. is supported by the European Research Council (ERC-617457- PHYLOCANCER), the Spanish Ministry of Economy and Competitiveness (BFU2015-63774-P) and the Education, Culture and University Development Department of the Galician Government. K.S.A. is supported in part by the Breast Cancer Research Foundation and NCI R21CA196460. C.S. is supported by the Royal Society, Cancer Research UK (FC001169), the UK Medical Research Council (FC001169), and the Wellcome Trust (FC001169), NovoNordisk Foundation (ID 16584), the Breast Cancer Research Foundation (BCRF), the European Research Council (THESEUS) and Marie Curie Network PloidyNet. T.A.G. is a Cancer Research UK fellow and a Wellcome Trust funded Investigator. E.S.H. is supported by R01 CA185138-01 and W81XWH-14-1-0473. M.Gerlinger is supported by Cancer Research UK and The Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre. M.Ge., M.Gr., Y.Y., and A.So. were also supported in part by the Wellcome Trust [105104/Z/14/Z]. J.D.S. holds the Edward B. Clark, MD Chair in Pediatric Research, and is supported by the Primary Children's Hospital (PCH) Pediatric Cancer Research Program, funded by the Intermountain Healthcare Foundation and the PCH Foundation. A.S. is supported by the Chris Rokos Fellowship in Evolution and Cancer. Y.Y. is a Cancer Research UK fellow and supported by The Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre. E.S.H. was supported in part by PCORI grants 1505–30497 and 1503–29572, NIH grants R01 CA185138, T32 CA093245, and U10 CA180857, CDMRP Breast Cancer Research Program Award BC132057, a CRUK Grand Challenge grant, and the Breast Cancer Research Foundation. A.R.A.A. was funded in part by NIH grant U01CA151924. A.R.A.A., R.G. and J.S.B. were funded in part by NIH grant U54CA193489

Diskussion um Krebscluster - Spannungsfeld zwischen politischer Erwartung und methodischer Machbarkeit Erfahrungsbericht zur Auswertung des EKN zur Samtgemeinde (SG) Asse

As cohabitation among unmarried couples becomes more common in the United States, a most pressing challenge facing inheritance law scholars, practitioners and others who concern themselves with the development of inheritance law is to craft reforms that would, if implemented, better serve non-marital families while at the same time maintain a reasonable ease of administration of estates. One area in urgent need of such reform is intestacy law. Current intestacy law generally does not reflect as well as it could the way Americans today structure their family lives. For example, the intestacy statutes of forty-seven states make no provision for the survivor of a non-marital committed partnership. This article proposes to change that. Professor Spitko has structured an intestacy statute that looks beyond the attributed intent of the decedent in order to protect those surviving committed partners who contributed significantly to the decedent\u27s wealth or physical well-being or who sacrificed career opportunities for the good of the partnership. To implement these reciprocity and reliance values, Professor Spitko identifies twenty-three factors (the multi-factor test) that a court should use to qualify a committed partner for the purposes of the intestacy statute. His proposal also sets forth an accrual schedule that determines the size of the surviving committed partner\u27s intestate share based on the duration of the partnership. Professor Spitko further proposes to give an intestate share to the survivor of a committed partnership that fractured prior to the decedent\u27s death if, under the circumstances, the survivor\u27s reciprocity or reliance interests should be vindicated. And he proposes to alter the rules for standing to challenge a committed partner\u27s will in order to minimize the uncertainty that the proposal necessarily would introduce into the probate process