Link to publication Citation for published version (APA)

UvA-DARE is a service provided by the library of the University of Amsterdam (http://dare.uva.nl) UvA-DARE (Digital Academic Repository) 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency is caused by mutations in the HADH2 gene Ofman, R.; Ruiter, J.P.N.; Feenstra, M.; Duran, M.; Poll-The, B-T.; Zschocke, J.; Ensenauer, R.; Lehnert, W.; Sass, J.O.; Sperl, W.; Wanders, R.J.A

Challenging medical students with an interim assessment: a positive effect on formal examination score in a randomized controlled study

Until now, positive effects of assessment at a medical curriculum level have not been demonstrated. This study was performed to determine whether an interim assessment, taken during a small group work session of an ongoing biomedical course, results in students’ increased performance at the formal course examination. A randomized controlled trial was set up, with an interim assessment without explicit feedback as intervention. It was performed during a regular biomedical Bachelor course of 4 weeks on General Pathology at the Radboud University Nijmegen Medical Centre. Participants were 326 medical and 91 biomedical science students divided into three study arms: arm Intervention-1 (I-1) receiving one interim assessment; arm I-2 receiving two interim assessments, and control arm C, receiving no interim assessment. The study arms were stratified for gender and study discipline. The interim assessment consisted of seven multiple-choice questions on tumour pathology. Main outcome measures were overall score of the formal examination (scale 1–10), and the subscore of the questions on tumour pathology (scale 1–10). We found that students who underwent an interim assessment (arm I) had a 0.29-point (scale 1–10) higher score on the formal examination than the control group (p = 0.037). For the questions in the formal examination on tumour pathology the score amounted to 0.47 points higher (p = 0.007), whereas it was 0.17 points higher for the questions on topics related to the previous 3 weeks. No differences in formal examination score were found between arms I-1 and I-2 (p = 0.817). These findings suggest that an interim assessment during a small group work session in a randomized study setting stimulates students to increase their formal examination score

Using Intratumor Heterogeneity of Immunohistochemistry Biomarkers to Classify Laryngeal and Hypopharyngeal Tumors Based on Histologic Features

Haralick texture features are used to quantify the spatial distribution of signal intensities within an image. In this study, the heterogeneity of proliferation (Ki-67 expression) and immune cells (CD45 expression) within tumors was quantified and used to classify histologic characteristics of larynx and hypopharynx carcinomas. Of 21 laryngectomy specimens, 74 whole-mount tumor slides were scored on histologic characteristics. Ki-67 and CD45 immunohistochemistry was performed, and all sections were digitized. The tumor area was annotated in QuPath. Haralick features independent of the diaminobenzidine intensity were extracted from the isolated diaminobenzidine signal to quantify intratumor heterogeneity. Haralick features from both Ki-67 and CD45 were used as input for a principal component analysis. A linear support vector machine was fitted to the first 4 principal components for classification and validated with a leave-one-patient-out cross-validation method. Significant differences in individual Haralick features were found between cohesive and noncohesive tumors for CD45 (angular second motion: P =.03, inverse difference moment: P =.009, and entropy: P =.02) and between the larynx and hypopharynx tumors for both CD45 (angular second motion: P =.03, inverse difference moment: P =.007, and entropy: P =.005) and Ki-67 (correlation: P =.003). Therefore, these features were used for classification. The linear classifier resulted in a classification accuracy of 85% for site of origin and 81% for growth pattern. A leave-one-patient-out cross-validation resulted in an error rate of 0.27 and 0.35 for both classifiers, respectively. In conclusion, we show a method to quantify intratumor heterogeneity of immunohistochemistry biomarkers using Haralick features. This study also shows the feasibility of using these features to classify tumors by histologic characteristics. The classifiers created in this study are a proof of concept because more data are needed to create robust classifiers, but the method shows potential for automated tumor classification.</p

A Case Concerning Children's False Memories of Abuse: Recommendations Regarding Expert Witness Work

Expert witnesses can play a major role in legal cases concerning the reliability of statements. Abuse cases frequently contain only the memories of eyewitnesses/victims without the presence of physical evidence. Here, it is of the utmost importance that expert witnesses use scientific evidence for their expert opinion. In this case report, a case is described in which 20 children reported being sexually abused by the same teachers at their elementary school. The investigative steps that were taken by the police and school authorities are reviewed, including how they probably affected memory. In order to provide a sound expert opinion regarding the reliability of these statements, three recommendations are proposed. To reduce the effect of confirmation bias and increase objectivity, it is argued that expert witnesses’ reports should contain alternative scenarios, be checked by another expert, and focus on the origin and context of the first statement

Antenatal atazanavir: a retrospective analysis of pregnancies exposed to atazanavir.

INTRODUCTION: There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. METHODS: A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. RESULTS: There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), "preconception" atazanavir exposure; 27 started atazanavir-based cART as "first-line" during the pregnancy; and 29 "switched" to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. CONCLUSIONS: These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy

IRAS F02044+0957: radio source in interacting system of galaxies

The steep spectrum of IRAS F02044+0957 was obtained with the RATAN-600 radio telescope at four frequencies. Optical spectroscopy of the system components, was carried out with the 2.1m telescope of the Guillermo Haro Observatory. Observational data allow us to conclude that this object is a pair of interacting galaxies, a LINER and a HII galaxy, at $z=0.093$.Comment: 2 pages, 2 EPS-figures, uses newpasp.sty. To appear in Proc. IAU Colloq. 184, AGN Surveys, ed. R. F. Green, E. Ye. Khachikian, & D. B. Sanders (San Francisco: ASP

Constraining Type Ia Supernovae progenitors from three years of SNLS data

While it is generally accepted that Type Ia supernovae are the result of the explosion of a carbon-oxygen White Dwarf accreting mass in a binary system, the details of their genesis still elude us, and the nature of the binary companion is uncertain. Kasen (2010) points out that the presence of a non-degenerate companion in the progenitor system could leave an observable trace: a flux excess in the early rise portion of the lightcurve caused by the ejecta impact with the companion itself. This excess would be observable only under favorable viewing angles, and its intensity depends on the nature of the companion. We searched for the signature of a non-degenerate companion in three years of Supernova Legacy Survey data by generating synthetic lightcurves accounting for the effects of shocking and comparing true and synthetic time series with Kolmogorov-Smirnov tests. Our most constraining result comes from noting that the shocking effect is more prominent in rest-frame B than V band: we rule out a contribution from white dwarf-red giant binary systems to Type Ia supernova explosions greater than 10% at 2 sigma, and than 20% at 3 sigma level.Comment: 14 pages, 15 figures, resubmitted to ApJ, figure 15 modifie

MARS spectral molecular imaging of lamb tissue: data collection and image analysis

Spectral molecular imaging is a new imaging technique able to discriminate and quantify different components of tissue simultaneously at high spatial and high energy resolution. Our MARS scanner is an x-ray based small animal CT system designed to be used in the diagnostic energy range (20 to 140 keV). In this paper, we demonstrate the use of the MARS scanner, equipped with the Medipix3RX spectroscopic photon-processing detector, to discriminate fat, calcium, and water in tissue. We present data collected from a sample of lamb meat including bone as an illustrative example of human tissue imaging. The data is analyzed using our 3D Algebraic Reconstruction Algorithm (MARS-ART) and by material decomposition based on a constrained linear least squares algorithm. The results presented here clearly show the quantification of lipid-like, water-like and bone-like components of tissue. However, it is also clear to us that better algorithms could extract more information of clinical interest from our data. Because we are one of the first to present data from multi-energy photon-processing small animal CT systems, we make the raw, partial and fully processed data available with the intention that others can analyze it using their familiar routines. The raw, partially processed and fully processed data of lamb tissue along with the phantom calibration data can be found at [http://hdl.handle.net/10092/8531].Comment: 11 pages, 6 fig