Notitie Denktank Overlijdensschade. Nieuwe richting benadering en berekening overlijdensschade

In 2009 is een werkgroep onder de naam Denktank Overlijdensschade gestart met het bestuderen van een ander, aan de huidige tijd aangepast model voor de berekening van overlijdensschade. Doelstelling was te komen tot een, ook voor nabestaanden, transparantie systematiek welke recht doet aan de vorderingsgerechtigdheid van de nabestaanden. In 2014 heeft de Denktank Overlijdensschade haar werkzaamheden voltooid met het opleveren van een nieuwe rekenmethodiek. In deze Notitie wordt beschreven hoe de Denktank tot deze nieuwe benadering van het berekenen van overlijdensschade is gekomen, welke onderzoeken daaraan ten grondslag liggen en wat de uiteindelijke rekenregel is, die nu voorgesteld wordt. Kern van de nieuwe methodiek is het uitgangspunt dat het gezin als economische eenheid wordt beschouwd, voor én na het overlijden

Functional Characterization of Promoter Variants of the Adiponectin Gene Complemented by Epidemiological Data

# These authors contributed equally to the work. *Corresponding author

Contribution of Transcription Factor Binding Site Motif Variants to Condition-Specific Gene Expression Patterns in Budding Yeast

It is now experimentally well known that variant sequences of a cis transcription factor binding site motif can contribute to differential regulation of genes. We characterize the relationship between motif variants and gene expression by analyzing expression microarray data and binding site predictions. To accomplish this, we statistically detect motif variants with effects that differ among environments. Such environmental specificity may be due to either affinity differences between variants or, more likely, differential interactions of TFs bound to these variants with cofactors, and with differential presence of cofactors across environments. We examine conservation of functional variants across four Saccharomyces species, and find that about a third of transcription factors have target genes that are differentially expressed in a condition-specific manner that is correlated with the nucleotide at variant motif positions. We find good correspondence between our results and some cases in the experimental literature (Reb1, Sum1, Mcm1, and Rap1). These results and growing consensus in the literature indicates that motif variants may often be functionally distinct, that this may be observed in genomic data, and that variants play an important role in condition-specific gene regulation

Silencing and Nuclear Repositioning of the λ5 Gene Locus at the Pre-B Cell Stage Requires Aiolos and OBF-1

The chromatin regulator Aiolos and the transcriptional coactivator OBF-1 have been implicated in regulating aspects of B cell maturation and activation. Mice lacking either of these factors have a largely normal early B cell development. However, when both factors are eliminated simultaneously a block is uncovered at the transition between pre-B and immature B cells, indicating that these proteins exert a critical function in developing B lymphocytes. In mice deficient for Aiolos and OBF-1, the numbers of immature B cells are reduced, small pre-BII cells are increased and a significant impairment in immunoglobulin light chain DNA rearrangement is observed. We identified genes whose expression is deregulated in the pre-B cell compartment of these mice. In particular, we found that components of the pre-BCR, such as the surrogate light chain genes λ5 and VpreB, fail to be efficiently silenced in double-mutant mice. Strikingly, developmentally regulated nuclear repositioning of the λ5 gene is impaired in pre-B cells lacking OBF-1 and Aiolos. These studies uncover a novel role for OBF-1 and Aiolos in controlling the transcription and nuclear organization of genes involved in pre-BCR function

Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: The OPTIPARK open-label study

BACKGROUND: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. METHODS: OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). RESULTS: Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. CONCLUSIONS: Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. TRIAL REGISTRATION: Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Strahlenschutzerfahrungen beim Umbau des Forschungsreaktors FRJ-1 (MERLIN)

Um die Experimentiermöglichkeiten an dem Forschungsreaktor FRJ-1 verbessern zu können, waren Umbauarbeiten im Reaktortank vorzunehmen. Diese Arbeiten erfolgten, nachdem der Reaktor bereits einige Jahre in Betrieb gewesen war und demzufolge seine Bauteile, besonders im Innern des Tanks, sich weitgehend aktiviert hatten. Zum Schutze der an dem Umbau beteiligten Personen, waren daher umfassende Strahlenschutzmaßnahmen erforderlich. Es wird über die Dosisleistungs-, Kontaminations- und Luftaktivitätsmessungen berichtet, die vor Beginn des Umbaues zur Beurteilung der Strahlenschutzverhältnisse im Reaktortank durchgeführt wurden. Außerdem werden die Schutzmaßnahmen für das am Umbau beteiligte Personal beschrieben. Zum Schluß des Berichtes wird gezeigt, daß ein strahlenschutzmäßig sicherer Leistungsbetrieb des Reaktors nach erfolgtem Umbau gewährleistet ist

FEV HiFORS: A new passenger car Diesel injector with continuous rate shaping for 2500 bar injection pressure

This paper presents the HiFORS continuously rate shaping injector for injection pressures of 2500 bar and above developed by FEVGmbH and the Institute for Combustion Engines, RWTH Aachen University. The development process from concept definition to hydraulic and deisgn layout, material choice and manufacturing is discussed. The hydraulic operating properties are verified by injection test rig investigations. Optical investigations are conducted in an optically accessible high pressure, high temperature chamber using shadowgraphy and OH chemoluminescence detection, thereby capturing both liquid and gaseous penetration as well as combustion areas. Single cylinder investigations are carried out at a 0.4 dm3 research engine in different operating points from low part load to full load. Compared to a serial production piezo injector, base measurements using conventional square injection profiles already show reduced combustion noise at improved NOx-soot trade-off as well as lowered HC and CO emissions. Detailed investigations at part load operating points explore the potential of different continuous rate shaping patterns, while the injector’s high injection pressure capability of up to 2500 bar and its influence on engine performance is tested at full load operation points

Überprüfung der Strahlenschutzsicherheit des Reaktors FRJ-1 (Merlin) nach der Leistungserhöhung auf zehn Megawatt

Die thermische Leistung des Forschungsreaktors FRJ-1, einem offenen Tankreaktor, bei dem Leichtwasser als Kühlmittel und Moderator dient, ist von 5 auf 10 Megawatt erhöht worden (11. Es wird die Überprüfung der Strahlenschutzsicherheit des Reaktors beschrieben, die im Rahmen des Anfahrprogramms bei der ersten Leistungserhöhung vorgenommen wurde. Hierzu mußten die durch $\gamma$- und Neutronenstrahlung hervorgerufenen Dosisleistungen gemessen sowie die Konzentrationen an radioaktiven Gasen und Aerosolenin der Hallenluft und in der Abluft des Reaktors ermittelt werden. Spezielle Untersuchungen dienten außerdem dazu, den Einfluß einer Wärmeinversionsschicht im Tankwasser auf die auf dem Reaktortop vorhandene Strahlung zu bestimmen. Die Messungen, die in den Monaten Oktober bis Dezember 1971 durchgeführt wurden, zeigten, daß ein strahlenschutzmäßig sicherer Betrieb des Reaktors bis zu einer Leistung von 10 Megawatt gewährleistet ist. Außerdem werden die Maßnahmen beschrieben, die zur Wahrung der Strahlenschutzsicherheit notwendig waren, als der Reaktor für die Leistungserhöhung umgebaut wurde. Zum Schluß wird über experimentelle Untersuchungen berichtet, die für eine Störfallanalyse vorgenommen wurden und Aufschluß über die Strahlenbelastung ergaben, die innerhalb der Reaktorhalle und in der Umgebung bei einem Kühlmittelverlust des Reaktors zu erwarten sind. Es konnte dabei nachgewiesen werden, daß selbst bei dem äußerst unwahrscheinlichen Fall eines Verlustes des Primärwassers um mehr als 65 % des Tankinhaltes bei einem mit hochaktiven Brennelementen vollbeladenen Reaktor noch keine ernsthafte Personengefährdung auftritt