Exploring multivariate clinical chemical routine data concerning three major disease groups

In preparation for multivariate analysis, an exploratory study has been undertaken to investigate the relative position, separability, homogeneity and shape of three major disease groups, using data from a clinical chemical routine package

Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding

Acknowledgments: We thank all the women who participated in this trial; the participating general practitioners, gynecologists, and hospitals; the research nurses; and the staff of the Dutch Consortium for Studies in Women’s Health and Reproduction.Peer reviewedPublisher PD

A novel seven-octapeptide repeat insertion in the prion protein gene (PRNP) in a Dutch pedigree with Gerstmann–Sträussler–Scheinker disease phenotype: comparison with similar cases from the literature

Human prion diseases can be sporadic, inherited or acquired by infection and show considerable phenotypic heterogeneity. We describe the clinical, histopathological and pathological prion protein (PrPSc) characteristics of a Dutch family with a novel 7-octapeptide repeat insertion (7-OPRI) in PRNP, the gene encoding the prion protein (PrP). Clinical features were available in four, neuropathological features in three and biochemical characteristics in two members of this family. The clinical phenotype was characterized by slowly progressive cognitive decline, personality change, lethargy, depression with anxiety and panic attacks, apraxia and a hypokinetic-rigid syndrome. Neuropathological findings consisted of numerous multi- and unicentric amyloid plaques throughout the cerebrum and cerebellum with varying degrees of spongiform degeneration. Genetic and molecular studies were performed in two male family members. One of them was homozygous for valine and the other heterozygous for methionine and valine at codon 129 of PRNP. Sequence analysis identified a novel 168 bp insertion [R2–R2–R2–R2–R3g–R2–R2] in the octapeptide repeat region of PRNP. Both patients carried the mutation on the allele with valine at codon 129. Western blot analysis showed type 1 PrPSc in both patients and detected a smaller ~8 kDa PrPSc fragment in the cerebellum in one patient. The features of this Dutch kindred define an unusual neuropathological phenotype and a novel PRNP haplotype among the previously documented 7-OPRI mutations, further expanding the spectrum of genotype–phenotype correlations in inherited prion diseases

Transcriptional characterization of human megakaryocyte polyploidization and lineage commitment

Funder: National Institute for Health Research; Id: http://dx.doi.org/10.13039/501100014338Funder: NHS Blood and Transplant; Id: http://dx.doi.org/10.13039/100009033Funder: Bristol‐Myers Squibb; Id: http://dx.doi.org/10.13039/100002491Funder: European Commission; Id: http://dx.doi.org/10.13039/100013273Abstract: Background: Megakaryocytes (MKs) originate from cells immuno‐phenotypically indistinguishable from hematopoietic stem cells (HSCs), bypassing intermediate progenitors. They mature within the adult bone marrow and release platelets into the circulation. Until now, there have been no transcriptional studies of primary human bone marrow MKs. Objectives: To characterize MKs and HSCs from human bone marrow using single‐cell RNA sequencing, to investigate MK lineage commitment, maturation steps, and thrombopoiesis. Results: We show that MKs at different levels of polyploidization exhibit distinct transcriptional states. Although high levels of platelet‐specific gene expression occur in the lower ploidy classes, as polyploidization increases, gene expression is redirected toward translation and posttranslational processing transcriptional programs, in preparation for thrombopoiesis. Our findings are in keeping with studies of MK ultrastructure and supersede evidence generated using in vitro cultured MKs. Additionally, by analyzing transcriptional signatures of a single HSC, we identify two MK‐biased HSC subpopulations exhibiting unique differentiation kinetics. We show that human bone marrow MKs originate from these HSC subpopulations, supporting the notion that they display priming for MK differentiation. Finally, to investigate transcriptional changes in MKs associated with stress thrombopoiesis, we analyzed bone marrow MKs from individuals with recent myocardial infarction and found a specific gene expression signature. Our data support the modulation of MK differentiation in this thrombotic state. Conclusions: Here, we use single‐cell sequencing for the first time to characterize the human bone marrow MK transcriptome at different levels of polyploidization and investigate their differentiation from the HSC

Can hysterosalpingo-foam sonography replace hysterosalpingography as first-choice tubal patency test? A randomized non-inferiority trial

Funding Information: The FOAM study was an investigator-initiated study funded by ZonMw, The Netherlands organization for Health Research and Development (project number 837001504). ZonMw funded the whole project. IQ Medical Ventures provided the ExEm-foamVR kits free of charge. The funders had no role in study design, collection, analysis and interpretation of the data. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.Peer reviewedPublisher PD

Comparison of VMAT and IMRT strategies for cervical cancer patients using automated planning

Background and purpose: In a published study on cervical cancer, 5-beam IMRT was inferior to single arc VMAT. Here we compare 9,12, and 20 beam IMRT with single and dual arc VMAT. Material and methods: For each of 10 patients, automated plan generation with the in-house Erasmusi-Cycle optimizer was used to assist an expert planner in generating the five plans with the clinical TPS. Results: For each patient, all plans were clinically acceptable with a high and similar PTV coverage. OAR sparing increased when going from 9 to 12 to 20 IMRT beams, and from single to dual arc VMAT. For all patients, 12 and 20 beam IMRT were superior to single and dual arc VMAT, with substantial variations in gain among the study patients. As expected, delivery of VMAT plans was significantly faster than delivery of IMRT plans. Conclusions: Often reported increased plan quality for VMAT compared to IMRT has not been observed for cervical cancer. Twenty and 12 beam IMRT plans had a higher quality than single and dual arc VMAT. For individual patients, the optimal delivery technique depends on a complex trade-off between plan quality and treatment time that may change with introduction of faster delivery systems. (c) 2015 Elsevier Ireland Ltd. All rights reserved

Motif and motive in the first thirty cantos of Ezra Pound /

Diss. lic. taal- en letterkunde: Germaanse tale

Beter beheer met BIM: van informatiemodel naar informatiemanagement

Deze publicatie is de rapportage van het RAAKProgramma BIMming business van de Hogeschool van Amsterdam (HvA)