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Sökning: WFRF:(de Graaff E)

  • Resultat 1-9 av 9
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  • Glasbey, JC, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Underwood, J, et al. (författare)
  • Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
  • 2019
  • Ingår i: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:6, s. ofz198-
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
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  • de Graaff, M. A., et al. (författare)
  • Establishment and characterization of a new human myxoid liposarcoma cell line (DL-221) with the FUS-DDIT3 translocation
  • 2016
  • Ingår i: Laboratory Investigation. - : Elsevier BV. - 0023-6837. ; 96:8, s. 885-894
  • Tidskriftsartikel (refereegranskat)abstract
    • Myxoid liposarcoma has the pathognomonic fusion oncogene FUS-DDIT3 encoding a chimeric transcription factor. Metastatic risk is higher with an increased round cell component and has been linked to aberrations involving the IGFR/PI3K/AKT pathway. These molecular insights have yet to translate to targeted therapies, and the lack of experimental models is a major hindrance. We describe the initial in-depth characterization of a new cell line (DL-221) and establishment of a mouse xenograft model. The cell line DL-221 was derived from a metastatic pleural lesion showing myxoid and round cell histology. This newly established cell line was characterized for phenotypic properties and molecular cytogenetic profile, using PCR, COBRA-FISH, and western blot. Next-generation whole-exome sequencing was performed to further characterize the cell line and the parent tumor. NOD-SCID-IL2R gamma knockout mice were xenograft hosts. DL-221 cells grew an adhering monolayer and COBRA-FISH showed an aneuploid karyotype with t(12;16) (q13;p11) and several other rearrangements; RT-PCR demonstrated a FUS-DDIT3 fusion transcript type 1. Both the cell line and the original tumor harbored a TP53 compound heterozygous mutation in exon 4 and 7, and were wild-type for PIK3CA. Moreover, among the 1254 variants called by whole-exome sequencing, there was 77% concordance between the cell line and parent tumor. The recently described hotspot mutation in the TERT promoter region in myxoid liposarcomas was also found at C228T in DL-221. Xenografts suitable for additional preclinical studies were successfully established in mice after subcutaneous injection. The established DL-221 cell line is the only published available myxoid liposarcoma cell line that underwent spontaneous immortalization, without requiring SV40 transformation. The cell line and its xenograft model are unique and helpful tools to study the biology and novel potential-targeted treatment approaches for myxoid liposarcoma.
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  • Wit, J M., et al. (författare)
  • Personalized Approach to Growth Hormone Treatment: Clinical Use of Growth Prediction Models
  • 2013
  • Ingår i: Hormone Research in Paediatrics. - : Karger. - 1663-2818 .- 1663-2826. ; 79:5, s. 257-270
  • Forskningsöversikt (refereegranskat)abstract
    • The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic.
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  • Malmi, L., et al. (författare)
  • Developing a methodological taxonomy of EER papers
  • 2012
  • Ingår i: SEFI 40th Annual Conference 2012; Thessaloniki; Greece; 23 September 2012 through 26 September 2012. - 9782873520052
  • Konferensbidrag (refereegranskat)abstract
    • Engineering Education Research (EER) is a wide and rich field of investigation [1]. It covers research on learning and teaching in all engineering disciplines as well as in the supporting disciplines, like physics, chemistry, computing and mathematics, which form the scientific basis of engineering research. Moreover, EER draws on theories and research methodologies from social sciences, like education, psychology and sociology to investigate the many-faced aspects of learning and teaching engineering. In order to get a better overview of the whole field, there is a need to look at both what is being researched and how the research is carried out. The authors of this paper met in connection to a series of meetings arranged by the SEFI working group EER and a series of workshops organised by Line B of the EU project EUGENE, and decided to collaborate on the construction of a taxonomy for EER from a European perspective. The overall aim is to develop a taxonomy for the how aspect of EER. More specifically, we aim to identify what kind of theoretical frameworks and research designs that are being used, what kind of data that is collected and how it is analysed in EER papers. Our current analysis focuses on published papers in two major European EER forums: European Journal of Engineering Education and the EER track in the SEFI conference, but the taxonomy can obviously be used to analyse any other EER papers. We hope that this work will better reveal the richness of the field, but also highlight approaches that could be used more often in EER. Moreover, the results can be used to inform authors about differences between various publication forums, and emerging methodological trends in research. Finally, we will also look at how different aspects of research have been reported in EER papers with a view to providing suggestions for improving research reporting. In this paper we describe the taxonomy and how it was developed. The results of the analysis will be reported elsewhere.
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