Erasmus University Rotterdam

About: Erasmus University Rotterdam is a education organization based out in Rotterdam, Zuid-Holland, Netherlands. It is known for research contribution in the topics: Population & Health care. The organization has 35466 authors who have published 91288 publications receiving 4510972 citations. The organization is also known as: EUR.

Development of an instrument for measuring different types of cognitive load

Abstract: According to cognitive load theory, instructions can impose three types of cognitive load on the learner: intrinsic load, extraneous load, and germane load. Proper measurement of the different types of cognitive load can help us understand why the effectiveness and efficiency of learning environments may differ as a function of instructional formats and learner characteristics. In this article, we present a ten-item instrument for the measurement of the three types of cognitive load. Principal component analysis on data from a lecture in statistics for PhD students (n = 56) in psychology and health sciences revealed a three-component solution, consistent with the types of load that the different items were intended to measure. This solution was confirmed by a confirmatory factor analysis of data from three lectures in statistics for different cohorts of bachelor students in the social and health sciences (ns = 171, 136, and 148), and received further support from a randomized experiment with university freshmen in the health sciences (n = 58).

Presence of Genetic Variants Among Young Men With Severe COVID-19.

Abstract: Importance Severe coronavirus disease 2019 (COVID-19) can occur in younger, predominantly male, patients without preexisting medical conditions. Some individuals may have primary immunodeficiencies that predispose to severe infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective To explore the presence of genetic variants associated with primary immunodeficiencies among young patients with COVID-19. Design, Setting, and Participants Case series of pairs of brothers without medical history meeting the selection criteria of young (age Exposure Severe COVID-19. Main Outcome and Measures Results of rapid clinical whole-exome sequencing, performed to identify a potential monogenic cause. Subsequently, basic genetic and immunological tests were performed in primary immune cells isolated from the patients and family members to characterize any immune defects. Results The 4 male patients had a mean age of 26 years (range, 21-32), with no history of major chronic disease. They were previously well before developing respiratory insufficiency due to severe COVID-19, requiring mechanical ventilation in the ICU. The mean duration of ventilatory support was 10 days (range, 9-11); the mean duration of ICU stay was 13 days (range, 10-16). One patient died. Rapid clinical whole-exome sequencing of the patients and segregation in available family members identified loss-of-function variants of the X-chromosomalTLR7.In members of family 1, a maternally inherited 4-nucleotide deletion was identified (c.2129_2132del; p.[Gln710Argfs*18]); the affected members of family 2 carried a missense variant (c.2383G>T; p.[Val795Phe]). In primary peripheral blood mononuclear cells from the patients, downstream type I interferon (IFN) signaling was transcriptionally downregulated, as measured by significantly decreased mRNA expression ofIRF7,IFNB1, andISG15on stimulation with the TLR7 agonist imiquimod as compared with family members and controls. The production of IFN-γ, a type II IFN, was decreased in patients in response to stimulation with imiquimod. Conclusions and Relevance In this case series of 4 young male patients with severe COVID-19, rare putative loss-of-function variants of X-chromosomalTLR7were identified that were associated with impaired type I and II IFN responses. These preliminary findings provide insights into the pathogenesis of COVID-19.

Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects.

Abstract: Detection of minimal residual disease (MRD) has prognostic value in many hematologic malignancies, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, and multiple myeloma. Quantitative MRD data can be obtained with real-time quantitative PCR (RQ-PCR) analysis of immunoglobulin and T-cell receptor gene rearrangements, breakpoint fusion regions of chromosome aberrations, fusion-gene transcripts, aberrant genes, or aberrantly expressed genes, their application being dependent on the type of disease. RQ-PCR analysis can be performed with SYBR Green I, hydrolysis (TaqMan) probes, or hybridization (LightCycler) probes, as detection system in several RQ-PCR instruments. Dependent on the type of MRD-PCR target, different types of oligonucleotides can be used for specific detection, such as an allele-specific oligonucleotide (ASO) probe, an ASO forward primer, an ASO reverse primer, or germline probe and primers. To assess the quantity and quality of the RNA/DNA, one or more control genes must be included. Finally, the interpretation of RQ-PCR MRD data needs standardized criteria and reporting of MRD data needs international uniformity. Several European networks have now been established and common guidelines for data analysis and for reporting of MRD data are being developed. These networks also include standardization of technology as well as regular quality control rounds, both being essential for the introduction of RQ-PCR-based MRD detection in multicenter clinical treatment protocols.

Euthanasia, Physician-Assisted Suicide, and Other Medical Practices Involving the End of Life in the Netherlands, 1990–1995

Abstract: Background In 1991 a new procedure for reporting physician-assisted deaths was introduced in the Netherlands that led to a tripling in the number of reported cases. In 1995, as part of an evaluation of this procedure, a nationwide study of euthanasia and other medical practices concerning the end of life was begun that was identical to a study conducted in 1990. Methods We conducted two studies, the first involving interviews with 405 physicians (general practitioners, nursing home physicians, and clinical specialists) and the second involving questionnaires mailed to the physicians attending 6060 deaths that were identified from death certificates. The response rates were 89 percent and 77 percent, respectively. Results Among the deaths studied, 2.3 percent of those in the interview study and 2.4 percent of those in the death-certificate study were estimated to have resulted from euthanasia, and 0.4 percent and 0.2 percent, respectively, resulted from physician-assisted suicide. In 0.7 percent of cases, ...

Pan-cancer whole-genome analyses of metastatic solid tumours

Abstract: Metastatic cancer is a major cause of death and is associated with poor treatment efficacy. A better understanding of the characteristics of late-stage cancer is required to help adapt personalized treatments, reduce overtreatment and improve outcomes. Here we describe the largest, to our knowledge, pan-cancer study of metastatic solid tumour genomes, including whole-genome sequencing data for 2,520 pairs of tumour and normal tissue, analysed at median depths of 106× and 38×, respectively, and surveying more than 70 million somatic variants. The characteristic mutations of metastatic lesions varied widely, with mutations that reflect those of the primary tumour types, and with high rates of whole-genome duplication events (56%). Individual metastatic lesions were relatively homogeneous, with the vast majority (96%) of driver mutations being clonal and up to 80% of tumour-suppressor genes being inactivated bi-allelically by different mutational mechanisms. Although metastatic tumour genomes showed similar mutational landscape and driver genes to primary tumours, we find characteristics that could contribute to responsiveness to therapy or resistance in individual patients. We implement an approach for the review of clinically relevant associations and their potential for actionability. For 62% of patients, we identify genetic variants that may be used to stratify patients towards therapies that either have been approved or are in clinical trials. This demonstrates the importance of comprehensive genomic tumour profiling for precision medicine in cancer. The mutational landscape of metastatic cancer genomes is analysed in a large-scale, pan-cancer study of metastatic solid tumours that includes whole-genome sequencing of 2,520 tumour–normal tissue pairs.