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

Different defibrillation strategies in survivors after out-of-hospital cardiac arrest

BACKGROUND: In the last decade, there has been a rapid increase in the dissemination of automated external defibrillators (AEDs) for prehospital defibrillation of out-of-hospital cardiac arrest patients. The aim of this study was to study the association between different defibrillation strategies on survival rates over time in Copenhagen, Stockholm, Western Sweden and Amsterdam, and the hypothesis was that non-EMS defibrillation increased over time and was associated with increased survival. METHODS: We performed a retrospective analysis of four prospectively collected cohorts of out-of-hospital cardiac arrest patients between 2008 and 2013. Emergency medical service (EMS)-witnessed arrests were excluded. RESULTS: A total of 22 453 out-of-hospital cardiac arrest patients with known survival status were identified, of whom 2957 (13%) survived at least 30 days postresuscitation. Of all survivors with a known defibrillation status, 2289 (81%) were defibrillated, 1349 (59%) were defibrillated by EMS, 454 (20%) were defibrillated by a first responder AED and 429 (19%) were defibrillated by an onsite AED and 57 (2%) were unknown. The percentage of survivors defibrillated by first responder AEDs (from 13% in 2008 to 26% in 2013, p<0.001 for trend) and onsite AEDs (from 14% in 2008 to 30% in 2013, p<0.001 for trend) increased. The increased use of these non-EMS AEDs was associated with the increase in survival rate of patients with a shockable initial rhythm. CONCLUSION: Survivors of out-of-hospital cardiac arrest are increasingly defibrillated by non-EMS AEDs. This increase is primarily due to a large increase in the use of onsite AEDs as well as an increase in first-responder defibrillation over time. Non-EMS defibrillation accounted for at least part of the increase in survival rate of patients with a shockable initial rhythm

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

Predictive value of amplitude spectrum area of ventricular fibrillation waveform in patients with acute or previous myocardial infarction in out-of-hospital cardiac arrest

Background: Amplitude spectrum area (AMSA) of ventricular fibrillation (VF) has been associated with survival from out-of-hospital cardiac arrest (OHCA). Ischemic heart disease has been shown to change AMSA. We studied whether the association between AMSA and survival changes with acute ST-elevation myocardial infarction (STEMI) as cause of the OHCA and/or previous MI. Methods: Multivariate logistic regression with log-transformed AMSA of first artifact-free VF segment was used to assess the association between AMSA and survival, according to presence of STEMI or previous MI, adjusting for resuscitation characteristics, medication use and comorbidities. Results: Of 716 VF-patients included from an OHCA-registry in the Netherlands, 328 (46%) had STEMI as cause of OHCA. Previous MI was present in 186 (26%) patients. Survival was 66%; neither previous MI (P = 0.11) nor STEMI (P = 0.78) altered survival. AMSA was a predictor of survival (ORadj: 1.52, 95%-CI: 1.28-1.82). STEMI was associated with lower AMSA (8.4 mV-Hz [3.7-16.5] vs. 12.3 mV-Hz [5.6-23.0]; P <0.001), but previous MI was not (9.5 mV-Hz [3.9-18.0] vs 10.6 mV-Hz [4.6-19.3]; P = 0.27). When predicting survival, there was no interaction between previous MI and AMSA (P = 0.14). STEMI and AMSA had a significant interaction (P = 0.002), whereby AMSA was no longer a predictor of survival (ORadj: 1.03, 95%-CI: 0.77-1.37) in STEMI-patients. In patients without STEMI, higher AMSA was associated with higher survival rates (ORadj: 1.80, 95%-CI: 1.39-2.35). Conclusions: The prognostic value of AMSA is altered by the presence of STEMI: while AMSA has strong predictive value in patients without STEMI, AMSA is not a predictor of survival in STEMI-patients. (C) 2017 The Authors. Published by Elsevier Ireland Lt

Predictive value of amplitude spectrum area of ventricular fibrillation waveform in patients with acute or previous myocardial infarction in out-of-hospital cardiac arrest

BACKGROUND: Amplitude spectrum area (AMSA) of ventricular fibrillation (VF) has been associated with survival from out-of-hospital cardiac arrest (OHCA). Ischemic heart disease has been shown to change AMSA. We studied whether the association between AMSA and survival changes with acute ST-elevation myocardial infarction (STEMI) as cause of the OHCA and/or previous MI. METHODS: Multivariate logistic regression with log-transformed AMSA of first artifact-free VF segment was used to assess the association between AMSA and survival, according to presence of STEMI or previous MI, adjusting for resuscitation characteristics, medication use and comorbidities. RESULTS: Of 716 VF-patients included from an OHCA-registry in the Netherlands, 328 (46%) had STEMI as cause of OHCA. Previous MI was present in 186 (26%) patients. Survival was 66%; neither previous MI (P=0.11) nor STEMI (P=0.78) altered survival. AMSA was a predictor of survival (ORadj: 1.52, 95%-CI: 1.28-1.82). STEMI was associated with lower AMSA (8.4mV-Hz [3.7-16.5] vs. 12.3mV-Hz [5.6-23.0]; P<0.001), but previous MI was not (9.5mV-Hz [3.9-18.0] vs 10.6mV-Hz [4.6-19.3]; P=0.27). When predicting survival, there was no interaction between previous MI and AMSA (P=0.14). STEMI and AMSA had a significant interaction (P=0.002), whereby AMSA was no longer a predictor of survival (ORadj: 1.03, 95%-CI: 0.77-1.37) in STEMI-patients. In patients without STEMI, higher AMSA was associated with higher survival rates (ORadj: 1.80, 95%-CI: 1.39-2.35). CONCLUSIONS: The prognostic value of AMSA is altered by the presence of STEMI: while AMSA has strong predictive value in patients without STEMI, AMSA is not a predictor of survival in STEMI-patients