50 research outputs found
Inactivation of wheat-germ aspartate transcarbamoylase by the arginine-specific reagent phenylglyoxal
Micropatterned nanocrystalline zinc oxide thin films obtained through metal-loaded hydrogels
Outcomes of Moral Case Deliberation - the development of an evaluation instrument for clinical ethics support (the Euro-MCD)
Background
Clinical ethics support, in particular Moral Case Deliberation, aims to support health care providers to manage ethically difficult situations. However, there is a lack of evaluation instruments regarding outcomes of clinical ethics support in general and regarding Moral Case Deliberation (MCD) in particular. There also is a lack of clarity and consensuses regarding which MCD outcomes are beneficial. In addition, MCD outcomes might be context-sensitive. Against this background, there is a need for a standardised but flexible outcome evaluation instrument. The aim of this study was to develop a multi-contextual evaluation instrument measuring health care providersâ experiences and perceived importance of outcomes of Moral Case Deliberation.
Methods
A multi-item instrument for assessing outcomes of Moral Case Deliberation (MCD) was constructed through an iterative process, founded on a literature review and modified through a multistep review by ethicists and health care providers. The instrument measures perceived importance of outcomes before and after MCD, as well as experienced outcomes during MCD and in daily work. A purposeful sample of 86 European participants contributed to a Delphi panel and content validity testing. The Delphi panel (nâ=â13), consisting of ethicists and ethics researchers, participated in three Delphi-rounds. Health care providers (nâ=â73) participated in the content validity testing through âthink-aloudâ interviews and a method using Content Validity Index.
Results
The development process resulted in the European Moral Case Deliberation Outcomes Instrument (Euro-MCD), which consists of two sections, one to be completed before a participantâs first MCD and the other after completing multiple MCDs. The instrument contains a few open-ended questions and 26 specific items with a corresponding rating/response scale representing various MCD outcomes. The items were categorised into the following six domains: Enhanced emotional support, Enhanced collaboration, Improved moral reflexivity, Improved moral attitude, Improvement on organizational level and Concrete results.
Conclusions
A tentative instrument has been developed that seems to cover main outcomes of Moral Case Deliberation. The next step will be to test the Euro-MCD in a field study
<em>GATA2</em> zinc finger 1 mutations associated with biallelic <em>CEBPA</em> mutations define a unique genetic entity of acute myeloid leukemia.
Cytogenetically normal acute myeloid leukemia (CN-AML) with biallelic CEBPA gene mutations (biCEPBA) represents a distinct disease entity with a favorable clinical outcome. So far, it is not known whether other genetic alterations cooperate with biCEBPA mutations during leukemogenesis. To identify additional mutations, we performed whole exome sequencing of 5 biCEBPA patients and detected somatic GATA2 zinc finger 1 (ZF1) mutations in 2 of 5 cases. Both GATA2 and CEBPA are transcription factors crucial for hematopoietic development. Inherited or acquired mutations in both genes have been associated with leukemogenesis. Further mutational screening detected novel GATA2 ZF1 mutations in 13 of 33 biCEBPA-positive CN-AML patients (13/33, 39.4%). No GATA2 mutations were found in 38 CN-AML patients with a monoallelic CEBPA mutation and in 89 CN-AML patients with wild-type CEBPA status. The presence of additional GATA2 mutations (n = 10) did not significantly influence the clinical outcome of 26 biCEBPA-positive patients. In reporter gene assays, all tested GATA2 ZF1 mutants showed reduced capacity to enhance CEBPA-mediated activation of transcription, suggesting that the GATA2 ZF1 mutations may collaborate with biCEPBA mutations to deregulate target genes during malignant transformation. We thus provide evidence for a genetically distinct subgroup of CN-AML. The German AML cooperative group trials 1999 and 2008 are registered with the identifiers NCT00266136 and NCT01382147 at www.clinicaltrials.gov. (Blood. 2012; 120(2): 395-403