Het gebruiksnormenstelsel, consequenties voor bedrijfsvoering en milieukwaliteit : Een eerste verkenning met modelbedrijven in Thema 5 (Maatregelenpakketten) van Programma 398

In 2006 komt het MINAS-stelsel te vervallen en wordt vervangen door een nieuw stelsel, dat momenteel wordt voorbereid en niet is gebaseerd op overschotten maar op gewasspecifieke gebruiksnormen. Deze verandering heeft gevolgen voor de bedrijfsvoering. In deze studie worden de resultaten in kaart gebracht van de consequenties van het nieuwe stelsel voor de sectoren akkerbouw, vollegrondsgroenten, bloembollen en boomteelt. Hierbij worden de consequenties beschreven in de vorm van te nemen maatregelen en bijbehorende kosten, de kosten van eventuele opbrengstderving en de effecten op het nitraatgehalte in het grondwater. De studie richt zich alleen op de zandgronden omdat daar de eerste problemen te verwachten zijn in de bedrijfsvoerin

Myoclonus in comatose patients with electrographic status epilepticus after cardiac arrest: corresponding EEG patterns, effects of treatment and outcomes

Objective: To clarify the significance of any form of myoclonus in comatose patients after cardiac arrest with rhythmic and periodic EEG patterns (RPPs) by analyzing associations between myoclonus and EEG pattern, response to anti-seizure medication and neurological outcome.Design: Post hoc analysis of the prospective randomized Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resus-citation (TELSTAR) trial.Setting: Eleven ICUs in the Netherlands and Belgium.Patients: One hundred and fifty-seven adult comatose post-cardiac arrest patients with RPPs on continuous EEG monitoring. Interventions: Anti-seizure medication vs no anti-seizure medication in addition to standard care.Measurements and Main Results: Of 157 patients, 98 (63%) had myoclonus at inclusion. Myoclonus was not associated with one specific RPP type. However, myoclonus was associated with a smaller probability of a continuous EEG background pattern (48% in patients with vs 75% without myoclonus, odds ratio (OR) 0.31; 95% confidence interval (CI) 0.16-0.64) and earlier onset of RPPs (24% vs 9% within 24 hours after cardiac arrest, OR 3.86;95% CI 1.64-9.11). Myoclonus was associated with poor outcome at three months, but not invariably so (poor neurological outcome in 96% vs 82%, p = 0.004). Anti-seizure medication did not improve outcome, regardless of myoclonus presence (6% good outcome in the intervention group vs 2% in the control group, OR 0.33; 95% CI 0.03-3.32).Conclusions: Myoclonus in comatose patients after cardiac arrest with RPPs is associated with poor outcome and discontinuous or suppressed EEG. However, presence of myoclonus does not interact with the effects of anti-seizure medication and cannot predict a poor outcome without false positives.Neurological Motor Disorder

H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts

BACKGROUND: H3K27ac histone acetylome changes contribute to the phenotypic response in heart diseases, particularly in end-stage heart failure. However, such epigenetic alterations have not been systematically investigated in remodeled non-failing human hearts. Therefore, valuable insight into cardiac dysfunction in early remodeling is lacking. This study aimed to reveal the acetylation changes of chromatin regions in response to myocardial remodeling and their correlations to transcriptional changes of neighboring genes. RESULTS: We detected chromatin regions with differential acetylation activity (DARs; Padj. < 0.05) between remodeled non-failing patient hearts and healthy donor hearts. The acetylation level of the chromatin region correlated with its RNA polymerase II occupancy level and the mRNA expression level of its adjacent gene per sample. Annotated genes from DARs were enriched in disease-related pathways, including fibrosis and cell metabolism regulation. DARs that change in the same direction have a tendency to cluster together, suggesting the well-reorganized chromatin architecture that facilitates the interactions of regulatory domains in response to myocardial remodeling. We further show the differences between the acetylation level and the mRNA expression level of cell-type-specific markers for cardiomyocytes and 11 non-myocyte cell types. Notably, we identified transcriptome factor (TF) binding motifs that were enriched in DARs and defined TFs that were predicted to bind to these motifs. We further showed 64 genes coding for these TFs that were differentially expressed in remodeled myocardium when compared with controls. CONCLUSIONS: Our study reveals extensive novel insight on myocardial remodeling at the DNA regulatory level. Differences between the acetylation level and the transcriptional level of cell-type-specific markers suggest additional mechanism(s) between acetylome and transcriptome. By integrating these two layers of epigenetic profiles, we further provide promising TF-encoding genes that could serve as master regulators of myocardial remodeling. Combined, our findings highlight the important role of chromatin regulatory signatures in understanding disease etiology

Generalized epileptiform discharges in postanoxic encephalopathy: Quantitative characterization in relation to outcome

Objective:\ud Electrographic status epilepticus is observed in 10–35% of patients with postanoxic encephalopathy. It remains unclear which electrographic seizure patterns indicate possible recovery, and which are a mere reflection of severe ischemic encephalopathy, where treatment would be futile. We aimed to identify quantitative electroencephalography (EEG) features with prognostic significance.\ud \ud Methods:\ud From continuous EEG recordings of 47 patients with generalized electrographic status epilepticus after cardiac arrest, 5-min epochs were selected every hour. Epochs were visually assessed and categorized into seven categories, including epileptiform discharges. Five quantitative measures were extracted, reflecting background continuity, discharge frequency, discharge periodicity, relative discharge power, and interdischarge waveform correlation. The best achieved outcome within 6 months after cardiac arrest was categorized as “good” (Cerebral Performance Category 1–2, i.e., no or moderate neurologic disability) or “poor” (CPC 3–5, i.e., severe disability, coma, or death).\ud \ud Results:\ud Ten patients (22%) had a good outcome. Status epilepticus in patients with good outcome started later (45 vs. 29 h after cardiac arrest, p < 0.001), more often ceased for at least 12 h (90% vs. 16%, p = 0.02), and was less often treated with antiepileptic drugs (30% vs. 73%, p = 0.02). Status epilepticus in patients with a good outcome always evolved from a continuous background pattern, as opposed to evolution from a discontinuous background pattern in 14 patients (38%) with a poor outcome. Epileptiform patterns of patients with good outcome had higher background continuity (1.00 vs. 0.83, p < 0.001), higher discharge frequency (1.63 vs. 0.90 Hz, p = 0.002), lower relative discharge power (0.29 vs. 0.40, p = 0.01), and lower discharge periodicity (0.32 vs. 0.45, p = 0.04).\ud \ud Significance:\ud Our results can be used to identify patients with possible recovery. We speculate that quantitative features associated with poor outcome reflect low neural network complexity, resulting from extensive ischemic damage

Treatment of electroencephalographic status epilepticus after cardiopulmonary resuscitation (TELSTAR): study protocol for a randomized controlled trial

Contains fulltext : 138739.pdf (publisher's version ) (Open Access)BACKGROUND: Electroencephalographic (EEG) status epilepticus is described in 10 to 35% of patients with postanoxic encephalopathy after successful cardiopulmonary resuscitation and is associated with case fatality rates of 90 to 100%. It is unclear whether these EEG patterns represent a condition to be treated with anticonvulsants to improve outcome, or an expression of severe ischemic damage, in which treatment is futile. METHODS/DESIGN: TELSTAR is a multicenter clinical trial with two parallel groups, randomized treatment allocation, open label treatment, and blinded endpoint evaluation (PROBE design). We aim to enroll 172 adult patients with postanoxic encephalopathy and electroencephalographic status epilepticus after successful cardiopulmonary resuscitation, admitted to the ICU, in whom continuous EEG monitoring is started within 24 hours after admission. Patients are randomly assigned to either medical treatment to suppress all electrographic seizure activity, or no treatment of electroencephalographic status epilepticus. Antiepileptic treatment is based on guidelines for treatment of overt status epilepticus and is started within 3 hours after the diagnosis. If status epilepticus returns during tapering of sedative medication after suppression of all epileptiform activity for 2 x 24 hours, it will be considered refractory. The primary outcome measure is neurological outcome defined as the Cerebral Performance Category (CPC) score at 3 months, dichotomized into 'good' (CPC 1 to 2 = no or moderate neurological disability) and 'poor' (CPC 3 to 5 = severe disability, coma, or death). Secondary outcome measures include mortality and, for patients surviving up to 12 months, cognitive functioning, health related quality of life, and depression. TRIAL REGISTRATION: Clinicaltrials.gov; NCT02056236. Date of registration: 4 February 2014

Relevance of somatosensory evoked potential amplitude after cardiac arrest

Contains fulltext : 220543.pdf (publisher's version ) (Open Access)Objective: We present relations of SSEP amplitude with neurological outcome and of SSEP amplitude with EEG amplitude in comatose patients after cardiac arrest. Methods: This is a post hoc analysis of a prospective cohort study in comatose patients after cardiac arrest. Amplitude of SSEP recordings obtained within 48-72 h, and EEG patterns obtained at 12 and 24h after cardiac arrest were related to good (CPC 1-2) or poor (CPC 3-5) outcome at 6 months. In 39% of the study population multiple SSEP measurements were performed. Additionally, SSEP amplitude was related to mean EEG amplitude. Results: We included 138 patients (77% poor outcome). Absent SSEP responses, a N20 amplitude <0.4 μV within 48-72 h, and suppressed or synchronous EEG with suppressed background at 12 or 24 h after cardiac arrest were invariably associated with a poor outcome. Combined, these tests reached a sensitivity for prediction of poor outcome up to 58 at 100% specificity. N20 amplitude increased with a mean of 0.55 μV per day in patients with a poor outcome, and remained stable with a good outcome. There was no statistically significant correlation between SSEP and EEG amplitudes in 182 combined SSEP and EEG measurements (R (2) < 0.01). Conclusions: N20 amplitude <0.4 μV is invariably associated with poor outcome. There is no correlation between SSEP and EEG amplitude. Significance: SSEP amplitude analysis may contribute to outcome prediction after cardiac arrest