Large Torque Variations in Two Soft Gamma Repeaters

We have monitored the pulse frequencies of the two soft gamma repeaters SGR 1806-20 and SGR 1900+14 through the beginning of year 2001 using primarily Rossi X-ray Timing Explorer Proportional Counter Array observations. In both sources, we observe large changes in the spin-down torque up to a factor of ~4, which persist for several months. Using long baseline phase-connected timing solutions as well as the overall frequency histories, we construct torque noise power spectra for each SGR. The power spectrum of each source is very red (power-law slope ~-3.5). The torque noise power levels are consistent with some accreting systems on time scales of ~1 year, yet the full power spectrum is much steeper in frequency than any known accreting source. To the best of our knowledge, torque noise power spectra with a comparably steep frequency dependence have only been seen in young, glitching radio pulsars (e.g. Vela). The observed changes in spin-down rate do not correlate with burst activity, therefore, the physical mechanisms behind each phenomenon are also likely unrelated. Within the context of the magnetar model, seismic activity cannot account for both the bursts and the long-term torque changes unless the seismically active regions are decoupled from one another.Comment: 26 pages, 11 figures included, accepted for publication in ApJ, analysis of torque noise power density spectra is revised from previous version and minor text changes were mad

Trimethylation of H3K27 during human cerebellar development in relation to medulloblastoma

Medulloblastoma (MB), the most common malignant childhood brain tumor, encompasses a collection of four clinically and molecularly distinct tumor subgroups, i.e. WNT, SHH, Group 3 and Group 4. These tumors are believed to originate from precursor cells during cerebellar development. Although the exact etiology of these brain tumors is not yet known, histone modifications are increasingly recognized as key events during cerebellum development and MB tumorigenesis. Recent studies show that key components involved in post-translational modifications of histone H3 lysine 27 (H3K27) are commonly deregulated in MB. In this descriptive study, we have investigated the trimethylation status of H3K27, as well as the expression of the H3K27 methylase EZH2 and demethylases KDM6A and KDM6B, during human cerebellum development in relation to MB. H3K27 Trimethylation status differed between the MB subgroups. Moreover, trimethylation of H3K27 and expression of its modifiers EZH2, KDM6A and KDM6B were detected in a spatio-temporal manner during development of the human cerebellum, with consistent high occurrence in the four proliferative zones, which are believed to harbor the precursor cells of the different MB subgroups. Our results suggest that H3K27 trimethylation in MB is deregulated by EZH2, KDM6A and KDM6B. Moreover, we provide evidence that during development of the human cerebellum H3K27me3 and its regulators are expressed in a spatio-temporal manner

Association of beta-blockers and first-registered heart rhythm in out-of-hospital cardiac arrest: real-world data from population-based cohorts across two European countries

AIMS: Conflicting results have been reported regarding the effect of beta-blockers on first-registered heart rhythm in out-of-hospital cardiac arrest (OHCA). We aimed to establish whether the use of beta-blockers influences first-registered rhythm in OHCA. METHODS AND RESULTS: We included patients with OHCA of presumed cardiac cause from two large independent OHCA-registries from Denmark and the Netherlands. Beta-blocker use was defined as exposure to either non-selective beta-blockers, β1-selective beta-blockers, or α-β-dual-receptor blockers within 90 days prior to OHCA. We calculated odds ratios (ORs) for the association of beta-blockers with first-registered heart rhythm using multivariable logistic regression. We identified 23 834 OHCA-patients in Denmark and 1584 in the Netherlands: 7022 (29.5%) and 519 (32.8%) were treated with beta-blockers, respectively. Use of non-selective beta-blockers, but not β1-selective blockers, was more often associated with non-shockable rhythm than no use of beta-blockers [Denmark: OR 1.93, 95% confidence interval (CI) 1.48-2.52; the Netherlands: OR 2.52, 95% CI 1.15-5.49]. Non-selective beta-blocker use was associated with higher proportion of pulseless electrical activity (PEA) than of shockable rhythm (OR 2.38, 95% CI 1.01-5.65); the association with asystole was of similar magnitude, although not statistically significant compared with shockable rhythm (OR 2.34, 95% CI 0.89-6.18; data on PEA and asystole were only available in the Netherlands). Use of α-β-dual-receptor blockers was significantly associated with non-shockable rhythm in Denmark (OR 1.21; 95% CI 1.03-1.42) and not significantly in the Netherlands (OR 1.37; 95% CI 0.61-3.07). CONCLUSION: Non-selective beta-blockers, but not β1-selective beta-blockers, are associated with non-shockable rhythm in OHCA

Automated external defibrillator and operator performance in out-of-hospital cardiac arrest

Aim: An increasing number of failing automated external defibrillators (AEDs) is reported: AEDs not giving a shock or other malfunction. We assessed to what extent AEDs are 'failing' and whether this had a device-related or operator-related cause. Methods: We studied analysis periods from AEDs used between January 2012 and December 2014. For each analysis period we assessed the correctness of the (no)-shock advice (sensitivity/specificity) and reasons for an incorrect (no)-shock advice. If no shock was delivered after a shock advice, we assessed the reason for no-shock delivery. Results: We analyzed 1114 AED recordings with 3310 analysis periods (1091 shock advices; 2219 no-shock advices). Sensitivity for coarse ventricular fibrillation was 99% and specificity for non-shockable rhythm detection 98%. The AED gave an incorrect shock advice in 4% (44/1091) of all shock advices, due to device-related (n = 15) and operator-related errors (n = 28) (one unknown). Of these 44 shock advices, only 2 shocks caused a rhythm change. One percent (26/2219) of all no-shock advices was incorrect due to device-related (n = 20) and operator-related errors (n = 6). In 5% (59/1091) of all shock advices, no shock was delivered: operator failed to deliver shock (n = 33), AED was removed (n = 17), operator pushed 'off' button (n = 8) and other (n = 1). Of the 1073 analysis periods with a shockable rhythm, 67 (6%) did not receive an AED shock. Conclusion: Errors associated with AED use are rare (4%) and when occurring are in 72% caused by the operator or circumstances of use. Fully automatic AEDs may prevent the majority of these errors. (C) 2017 The Author(s). Published by Elsevier Ireland Lt

Minimizing pre- and post-shock pauses during the use of an automatic external defibrillator by two different voice prompt protocols. A randomized controlled trial of a bundle of measures

Previous large retrospective analyses have found an association between duration of peri-shock pauses in cardiopulmonary resuscitation (CPR) and survival. In a randomized trial, we tested whether shortening these pauses improves survival after out-of-hospital cardiac arrest (OHCA). Patients with OHCA between May 2006 and January 2014 with shockable initial rhythm, treated by first responders, were randomized to two automated external defibrillator (AED) treatment protocols. In the control protocol AEDs performed post-shock analysis and prompted rescuers to a pulse check (Guidelines 2000). In the experimental protocol a 15s period of CPR during and after charging of the AED was added to the voice prompts and CPR was resumed immediately after defibrillation (modification of the Guidelines 2005). Survival was assessed at hospital admission and discharge. Of 1174 OHCA patients, 456 met the inclusion criteria: 227 were randomly assigned to the experimental protocol and 229 to the control protocol. The experimental group experienced shorter pre-shock pauses (6 [5-11]s vs. 20 [18-23]s; P <0.001), and shorter post-shock pauses (7 [6-9]s vs. 27 [16-34]s; P <0.001). Similar proportions of patients survived to hospital admission (experimental: 62% vs. 65%; RR [95%CI] 0.96 [0.83-1.10], P=0.51), and hospital discharge (experimental: 42% vs. 38%; RR [95%CI] 1.09 [0.87-1.37], P=0.46). In patients with OHCA and shockable initial rhythms, treatment with AEDs with the experimental protocol shortened pre-shock and post-shock CPR pauses, and increased overall CPR time, but did not improve survival to hospital admission or discharge. http://www.isrctn.com unique identifier: ISRCTN7225767

Transfer of essential AED information to treating hospital (TREAT)

Background: Defibrillation in out-of-hospital cardiac arrest (OHCA) is increasingly performed by using an Automated External Defibrillator (AED). Therefore presence of a shockable rhythm is recurrently only documented by the AED. However, AED-information is rarely available to the treating physician. Purpose: To determine (1) how often a shockable rhythm was recorded only in the AED; (2) if so, how often information that a shockable rhythm had been present reached the physician. Methods: Data on OHCA patients with (presumed) cardiac cause with an AED connected in the years 2012–2014 (Study period 1) and 2016 (Study period 2) in the Amsterdam Resuscitation Study (ARREST) database were collected. We determined how often only the AED had defibrillated. In these patients, we retrospectively analyzed EMS run sheets and hospital discharge letters to determine if a shockable rhythm and/or AED use was correctly noted. In Study period 2, we prospectively contacted the physicians to study whether AED defibrillation was known. Results: In Study period 1, of 2840 OHCA CPR attempts with (presumed) cardiac cause, 1521 (54%) patients had a shockable rhythm, with 356 patients (13%) receiving AED defibrillation only. Of these patients, 11 hospital discharge letters (4%) contained no information about a shockable rhythm. In Study period 2, 125/1128 patients (11%) received AED defibrillation only; of these, in two cases the shockable rhythm was unknown by the physician. Conclusion: In 11–13% of OHCAs, a shockable rhythm is only seen on the AED-ECG. Adequate transfer to the physician of vital AED-information is essential but not always accomplished