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Salivary duct carcinoma (SDC) is a subtype of salivary gland cancer with a dismal prognosis and a need for better prognostication and novel treatments. The aim of this national cohort study was to investigate clinical outcome, prognostic factors, androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression. SDC patients diagnosed between 1990 and 2014 were identified by the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA). Subsequently, medical records were evaluated and pathological diagnoses reviewed. Data were analyzed for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and prognostic factors. AR was evaluated by immunohistochemistry (IHC), HER2 by IHC and fluorescent in-situ hybridization. A total of 177 patients were included. The median age was 65 years, 75% were male. At diagnosis, 68% presented with lymph node metastases and 6% with distant metastases. Median OS, DFS and DMFS were 51, 23 and 26 months, respectively. In patients presenting without distant metastases, the absolute number of positive lymph nodes was associated with poor OS and DMFS in a multivariable analysis. AR and HER2 were positive in 161/168 (96%) and 44/153 (29%) tumors, respectively, and were not prognostic factors. SDC has a dismal prognosis with primary lymph node involvement in the majority of patients. The absolute number of lymph node metastases was found to be the only prognostic factor for DMFS and OS. AR expression and- to a lesser extent-HER2 expression hold promise for systemic treatment in the metastatic and eventually adjuvant setting.

Item does not contain fulltext Germline mutations in succinate dehydrogenase B (SDHB) predispose to hereditary paraganglioma (PGL) syndrome type 4. The risk of developing PGL or pheochromocytoma (PHEO) in SDHB mutation carriers is subject of recent debate. In the present nationwide cohort study of SDHB mutation carriers identified by the clinical genetics centers of the Netherlands, we have calculated the penetrance of SDHB associated tumors using a novel maximum likelihood estimator. This estimator addresses ascertainment bias and missing data on pedigree size and structure. A total of 195 SDHB mutation carriers were included, carrying 27 different SDHB mutations. The 2 most prevalent SDHB mutations were Dutch founder mutations: a deletion in exon 3 (31% of mutation carriers) and the c.423+1G>A mutation (24% of mutation carriers). One hundred and twelve carriers (57%) displayed no physical, radiological or biochemical evidence of PGL or PHEO. Fifty-four patients had a head and neck PGL (28%), 4 patients had a PHEO (2%), 26 patients an extra-adrenal PGL (13%). The overall penetrance of SDHB mutations is estimated to be 21% at age 50 and 42% at age 70 when adequately corrected for ascertainment. These estimates are lower than previously reported penetrance estimates of SDHB-linked cohorts. Similar disease risks are found for different SDHB germline mutations as well as for male and female SDHB mutation carriers.

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Item does not contain fulltext In screening and surveillance studies, event times are interval censored. Besides, screening tests are imperfect so that the interval at which an event takes place may be uncertain. We describe an expectation-maximization algorithm to find the nonparametric maximum likelihood estimator of the cumulative incidence function of an event based on screening test data. Our algorithm has a closed-form solution for the combined expectation and maximization step and is computationally undemanding. A simulation study indicated that the bias of the estimator tends to zero for large sample size, and its mean squared error is in general lower than the mean squared error of the estimator that assumes the screening test is perfect. We apply the algorithm to follow-up data from women treated for cervical precancer. Copyright (c) 2017 John Wiley & Sons, Ltd.

In retrospective studies involving recurrent events, it is common to select individuals based on their event history up to the time of selection. In this case, the ascertained subjects might not be representative for the target population, and the analysis should take the selection mechanism into account. The purpose of this paper is two-fold. First, to study what happens when the data analysis is not adjusted for the selection and second, to propose a corrected analysis. Under the Andersen–Gill and shared frailty regression models, we show that the estimators of covariate effects, incidence, and frailty variance can be biased if the ascertainment is ignored, and we show that with a simple adjustment of the likelihood, unbiased and consistent estimators are obtained. The proposed method is assessed by a simulation study and is illustrated on a data set comprising recurrent pneumothoraces.

We consider estimation and testing of linkage equilibrium from genotypic data on a random sample of sibs, such as monozygotic and dizygotic twins. We compute the maximum likelihood estimator with an EM-algorithm and a likelihood ratio statistic that takes the family structure into account. As we are interested in applying this to twin data we also allow observations on single children, so that monozygotic twins can be included. We allow non-zero recombination fraction between the loci of interest, so that linkage disequilibrium between both linked and unlinked loci can be tested. The EM-algorithm for computing the maximum likelihood estimator of the haplotype frequencies and the likelihood ratio test-statistic, are described in detail. It is shown that the usual estimators of haplotype frequencies based on ignoring that the sibs are related are inefficient, and the likelihood ratio test for testing that the loci are in linkage disequilibrium. © 2011 The Authors. Statistica Neerlandica © 2011 VVS.

New micro-level data have recently become available for three provinces of the The Netherlands for the period 1812-1912, which allow the study of the evolution of socio-economic differentials in infant and childhood mortality. The authors found significant differences in the levels of infant mortality by social group between the three provinces, and a wide variety in the pattern of social inequality. This showed the importance of the regional environment for the level of infant mortality in the nineteenth century. Contrary to expectations, strong social differences were also observed in neonatal mortality. Being born in an urban environment did not have a strongeffect on survival during the first year of birth. © Economic History Society 2005.

We consider the estimation of life length of people who were born in the seventeenth or eighteenth century in England. The data consist of a sequence of times of life events that is either ended by a time of death or is right-censored by an unobserved time of migration. We propose a semi parametric model for the data and use a maximum likelihood method to estimate the unknown parameters in this model. We prove the consistency of the maximum likelihood estimators and describe an algorithm to obtain the estimates numerically. We have applied the algorithm to data and the estimates found are presented.

This study describes the experiences with the FPLC-technique for the separation of actin from a mixture composed of some single muscle proteins like myosin, [alpha] - actinin, tropomyosin and troponin, and the quantitative analysis of actin.

Contains fulltext : 291366.pdf (Publisher’s version ) (Open Access) Radboud University, 20 april 2023 Promotor : Roes, C.B. Co-promotor : Jonker, M.A. viii, 337 p.

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