Large comparative databases provide the opportunity to identify distinct high and low scoring groups. In our study, language, work area, and profession were identified as important safety culture predictors. Years of experience in the hospital had only a small effect on safety culture perceptions.
Alzheimer’s disease (AD) is characterized by a long pre-clinical phase (20–30 years), during which significant brain pathology manifests itself. Disease mechanisms associated with pathological hallmarks remain elusive. Most processes associated with AD pathogenesis, such as inflammation, synaptic dysfunction, and hyper-phosphorylation of tau are dependent on protein kinase activity. The objective of this study was to determine the involvement of protein kinases in AD pathogenesis. Protein kinase activity was determined in postmortem hippocampal brain tissue of 60 patients at various stages of AD and 40 non-demented controls (Braak stages 0-VI) using a peptide-based microarray platform. We observed an overall decrease of protein kinase activity that correlated with disease progression. The phosphorylation of 96.7% of the serine/threonine peptides and 37.5% of the tyrosine peptides on the microarray decreased significantly with increased Braak stage (p-value <0.01). Decreased activity was evident at pre-clinical stages of AD pathology (Braak I-II). Increased phosphorylation was not observed for any peptide. STRING analysis in combination with pathway analysis and identification of kinases responsible for peptide phosphorylation showed the interactions between well-known proteins in AD pathology, including the Ephrin-receptor A1 (EphA1), a risk gene for AD, and sarcoma tyrosine kinase (Src), which is involved in memory formation. Additionally, kinases that have not previously been associated with AD were identified, e.g., protein tyrosine kinase 6 (PTK6/BRK), feline sarcoma oncogene kinase (FES), and fyn-associated tyrosine kinase (FRK). The identified protein kinases are new biomarkers and potential drug targets for early (pre-clinical) intervention.
U n c o r r e c t e d A u t h o r P r o o fAbstract. 18Background: Studies investigating the diagnostic accuracy of biomarkers for Alzheimer's disease (AD) are typically performed using the clinical diagnosis or amyloid- positron emission tomography as the reference test. However, neither can be considered a gold standard or a perfect reference test for AD. Not accounting for errors in the reference test is known to cause bias in the diagnostic accuracy of biomarkers.
Background: In Belgium, the federal government launched a national program to support hospitals for implementing quality and patient safety strategies. One of the main objectives in the federal program is the development of a safety culture. The purpose of this study was to examine to what extent the hospitals' safety culture evolved after participating in the federal program and to explore predictor variables of safety culture. Methods: In a cross-sectional follow-up design, safety culture was measured in the Belgian acute, psychiatric and long-term care hospitals using validated translations of the Hospital Survey on Patient Safety Culture in Flemish and French. For both nationwide measurements, hospitals were invited to participate in a benchmark research organized by an academic institution (in 2008 and 2012). Generalized Estimating Equations models were fitted to examine the effect of predictor variables on safety culture perceptions. Results: The Belgian safety culture database contains data from 115 827 respondents from 176 hospitals. For 111 hospitals that participated in both benchmarks it was possible to calculate changes in safety culture. The response rate for the second measurement (52.2%) was comparable to the response rate in the first measurement (51.0%). Improvements were observed for most safety culture dimensions with a major significant improvement for 'Management support for patient safety'. Although 'Handoffs and transitions' and 'Frequency of events reported' were key areas within the federal program, a decline was observed for these dimensions. Work area, staff position, language (regional context of hospital), hospital type and hospital statute were found to have important effects on safety culture perceptions. Hospital size and work experience, showed to have less effect on safety culture scores.
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