Cosmic ray electrons and positrons from discrete stochastic sources

The distances that galactic cosmic ray electrons and positrons can travel are severely limited by energy losses to at most a few kiloparsec, thereby rendering the local spectrum very sensitive to the exact distribution of sources in our galactic neighbourhood. However, due to our ignorance of the exact source distribution, we can only predict the spectrum stochastically. We argue that even in the case of a large number of sources the central limit theorem is not applicable, but that the standard deviation for the flux from a random source is divergent due to a long power law tail of the probability density. Instead, we compute the expectation value and characterise the scatter around it by quantiles of the probability density using a generalised central limit theorem in a fully analytical way. The uncertainty band is asymmetric about the expectation value and can become quite large for TeV energies. In particular, the predicted local spectrum is marginally consistent with the measurements by Fermi-LAT and HESS even without imposing spectral breaks or cut-offs at source. We conclude that this uncertainty has to be properly accounted for when predicting electron fluxes above a few hundred GeV from astrophysical sources.Comment: 16 pages, 8 figures; references and clarifying comment added; to appear in JCA

Taming impulsive high-frequency data using optimal sampling periods

Optimal sampling period selection for high-frequency data is at the core of financial instruments based on algorithmic trading. The unique features of such data, absent in data measured at lower frequencies, raise significant challenges to their statistical analysis and econometric modelling, especially in the case of heavy-tailed data exhibiting outliers and rare events much more frequently. To address this problem, this paper proposes a new methodology for optimal sampling period selection, which better adapts to heavy-tailed statistics of high-frequency financial data. In particular, the novel concept of the degree of impulsiveness (DoI) is introduced first based on alpha-stable distributions, as an alternative source of information for characterising a broad range of impulsive behaviours. Then, a DoI-based generalised volatility signature plot is defined, which is further employed for determining the optimal sampling period. The performance of our method is evaluated in the case of risk quantification for high-frequency indexes, demonstrating a significantly improved accuracy when compared against the well-established volatility-based approach. © 2023, The Author(s)

Adult advanced life support: Section 3 of the European Resuscitation Council Guidelines for Resuscitation 2015

Erweiterte lebensrettende Maßnahmen für Erwachsene („advanced life support“, ALS) kommen zum Einsatz, nachdem Basismaßnahmen zur Wiederbelebung („basic life support“, BLS) begonnen und, wenn sinnvoll, ein automatisierter externer Defibrillator (AED) verwendet wurde. Die Basismaßnahmen zur Wiederbelebung eines Erwachsenen und der Einsatz von AEDs wird in Kap. 2 ausgeführt. Basis- und erweiterte Maßnahmen sollen nahtlos ineinander übergehen, da erstere fortgeführt werden und sich mit den erweiterten überschneiden. Dieses Kapitel über die erweiterten Maßnahmen beinhaltet die Vermeidung des Kreislaufstillstands, spezielle Aspekte des außerklinischen ALS, den Start der innerklinischen Reanimation, den ALS-Algorithmus, die manuelle Defibrillation, das Atemwegsmanagement während der Reanimaton, Medikamente und ihre Anwendung während der Reanimation sowie die Behandlung von Periarrest-Arrhythmien. Es gibt zwei Änderungen in der äußeren Form dieser Leitlinien des Europäischen Rats für Wiederbelebung seit den Leitlinien von 2010: [1] Das Kapitel „Elektrotherapie“ [2] ist nicht mehr eigenständig, sondern Teil dieses Kapitels; und die Leitlinien zur Behandlung nach Reanimation sind in ein neues Kapitel ausgegliedert, welches die Bedeutung dieses letzten Glieds der Überlebenskette unterstreicht [3]. Diese Leitlinien basieren auf den International Liaison Committee on Resuscitation (ILCOR) Consensus on Science and Treatment Recommendations (CoSTR) für ALS von 2015 [4]. Die Überprüfung der ILCOR-Empfehlungen von 2015 konzentrierte sich auf 42 Themen, entsprechend der zeitlichen Abfolge der erweiterten Maßnahmen: Defibrillation, Atemwege, Oxygenierung und Ventilation, Kreislaufunterstützung und Überwachung und Einsatz von Medikamenten während der Reanimation. Für diese Leitlinien wurden die ILCOR-Empfehlungen durch ein gezieltes Literatur-Review ergänzt, welches von der ERC-ALS-Leitlinien Autorengruppe zu den Themen die nicht in den ILCOR-CoSTR-Empfehlungen von 2015 überarbeitet wurden erstellt wurde. Die Leitlinien wurden ausgearbeitet, von den ALS-Verfassern geprüft und abschließend von der ERC-Vollversammlung und dem ERC-Vorstand abgesegnet

Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review.

To assess the ability of clinical examination, blood biomarkers, electrophysiology, or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict poor neurological outcome, defined as death, vegetative state, or severe disability (CPC 3-5) at hospital discharge/1 month or later, in comatose adult survivors from cardiac arrest (CA). PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews (January 2013-April 2020) were searched. Sensitivity and false-positive rate (FPR) for each predictor were calculated. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed. Ninety-four studies (30,200 patients) were included. Bilaterally absent pupillary or corneal reflexes after day 4 from ROSC, high blood values of neuron-specific enolase from 24 h after ROSC, absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) or unequivocal seizures on electroencephalogram (EEG) from the day of ROSC, EEG background suppression or burst-suppression from 24 h after ROSC, diffuse cerebral oedema on brain CT from 2 h after ROSC, or reduced diffusion on brain MRI at 2-5 days after ROSC had 0% FPR for poor outcome in most studies. Risk of bias assessed using the QUIPS tool was high for all predictors. In comatose resuscitated patients, clinical, biochemical, neurophysiological, and radiological tests have a potential to predict poor neurological outcome with no false-positive predictions within the first week after CA. Guidelines should consider the methodological concerns and limited sensitivity for individual modalities. (PROSPERO CRD42019141169)

The impact of the Tracey judgment on the rates and outcomes of in-hospital cardiac arrests in UK hospitals participating in the National Cardiac Arrest Audit.

AIMS: The aim was to determine if the 17 June 2014 Tracey judgment regarding 'do not attempt cardiopulmonary resuscitation' decisions led to increases in the rate of in-hospital cardiac arrests resulting in a resuscitation attempt (IHCA) and/or proportion of resuscitation attempts deemed futile. METHOD: Using UK National Cardiac Arrest Audit data, the IHCA rate and proportion of resuscitation attempts deemed futile were compared for two periods (pre-judgment (01 July 2012 - 16 June 2014, inclusive) and post-judgment (01 July 2014 - 30 June 2016, inclusive)) using interrupted time series analyses. RESULTS: A total of 43,109 IHCAs (115 hospitals) were analysed. There were fewer IHCAs post- than pre-judgment (21,324 vs 21,785, respectively). The IHCA rate was declining over time before the judgment but there was an abrupt and statistically significant increase in the period immediately following the judgment (p<0.001). This was not sustained post-judgment. The proportion of resuscitation attempts deemed futile was smaller post-judgment than pre-judgment (8.2% vs 14.9%, respectively). The rate of attempts deemed futile decreased post-judgment (p<0.001). CONCLUSION: The IHCA rate increased immediately after the Tracey judgment while the proportion of resuscitation attempts deemed futile decreased. The precise mechanisms for these changes are unclear

Non-stoichiometric oxide and metal interfaces and reactions

We have employed a combination of experimental surface science techniques and density functional calculations to study the reduction of TiO2(110) surfaces through the doping with submonolayer transition metals. We concentrate on the role of Ti adatoms in self doping of rutile and contrast the behaviour to that of Cr. DFT+U calculations enable identification of probable adsorption structures and their spectroscopic characteristics. Adsorption of both metals leads to a broken symmetry and an asymmetric charge transfer localised around the defect site of a mixed localised/delocalised character. Charge transfer creates defect states with Ti 3d character in the band gap at similar to 1-eV binding energy. Cr adsorption, however, leads to a very large shift in the valence-band edge to higher binding energy and the creation of Cr 3d states at 2.8-eV binding energy. Low-temperature oxidation lifts the Ti-derived band-gap states and modifies the intensity of the Cr features, indicative of a change of oxidation state from Cr3+ to Cr4+. Higher temperature processing leads to a loss of Cr from the surface region, indicative of its substitution into the bulk

“All citizens of the world can save a life” — The World Restart a Heart (WRAH) initiative starts in 2018

“All citizens of the world can save a life”. With these words, the International Liaison Committee on Resuscitation (ILCOR) is launching the first global initiative – World Restart a Heart (WRAH) – to increase public awareness and therefore the rates of bystander cardiopulmonary resuscitation (CPR) for victims of cardiac arrest. In most of the cases, it takes too long for the emergency services to arrive on scene after the victim's collapse. Thus, the most effective way to increase survival and favourable outcome in cardiac arrest by two- to fourfold is early CPR by lay bystanders and by “first responders”. Lay bystander resuscitation rates, however, differ significantly across the world, ranging from 5 to 80%. If all countries could have high lay bystander resuscitation rates, this would help to save hundreds of thousands of lives every year. In order to achieve this goal, all seven ILCOR councils have agreed to participate in WRAH 2018. Besides schoolchildren education in CPR (“KIDS SAVE LIVES”), many other initiatives have already been developed in different parts of the world. ILCOR is keen for the WRAH initiative to be as inclusive as possible, and that it should happen every year on 16 October or as close to that day as possible. Besides recommending CPR training for children and adults, it is hoped that a unified global message will enable our policy makers to take action to address the inequalities in patient survival around the world.Revisión por pare

Purine nucleosides interfere with c-di-AMP levels and act as adjuvants to re-sensitize MRSA to β-lactam antibiotics

The purine-derived signaling molecules c-di-AMP and (p)ppGpp control mecA/PBP2a-mediated β-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) raise the possibility that purine availability can control antibiotic susceptibility. Consistent with this, exogenous guanosine and xanthosine, which are fluxed through the GTP branch of purine biosynthesis, were shown to significantly reduce MRSA β-lactam resistance. In contrast, adenosine (fluxed to ATP) significantly increased oxacillin resistance, whereas inosine (which can be fluxed to ATP and GTP via hypoxanthine) only marginally increased oxacillin susceptibility. Furthermore, mutations that interfere with de novo purine synthesis (pur operon), transport (NupG, PbuG, PbuX) and the salvage pathway (DeoD2, Hpt) increased β-lactam resistance in MRSA strain JE2. Increased resistance of a nupG mutant was not significantly reversed by guanosine, indicating that NupG is required for guanosine transport, which is required to reduce β-lactam resistance. Suppressor mutants resistant to oxacillin/guanosine combinations contained several purine salvage pathway mutations, including nupG and hpt. Guanosine significantly increased cell size and reduced levels of c-di-AMP, while inactivation of GdpP, the c-di-AMP phosphodiesterase negated the impact of guanosine on β-lactam susceptibility. PBP2a expression was unaffected in nupG or deoD2 mutants, suggesting that guanosine-induced β-lactam susceptibility may result from dysfunctional c-di-AMP-dependent osmoregulation. These data reveal the therapeutic potential of purine nucleosides, as β-lactam adjuvants that interfere with the normal activation of c-di-AMP are required for high-level β-lactam resistance in MRSA. IMPORTANCE The clinical burden of infections caused by antimicrobial resistant (AMR) pathogens is a leading threat to public health. Maintaining the effectiveness of existing antimicrobial drugs or finding ways to reintroduce drugs to which resistance is widespread is an important part of efforts to address the AMR crisis. Predominantly, the safest and most effective class of antibiotics are the β-lactams, which are no longer effective against methicillin-resistant Staphylococcus aureus (MRSA). Here, we report that the purine nucleosides guanosine and xanthosine have potent activity as adjuvants that can resensitize MRSA to oxacillin and other β-lactam antibiotics. Mechanistically, exposure of MRSA to these nucleosides significantly reduced the levels of the cyclic dinucleotide c-di-AMP, which is required for β-lactam resistance. Drugs derived from nucleotides are widely used in the treatment of cancer and viral infections highlighting the clinical potential of using purine nucleosides to restore or enhance the therapeutic effectiveness of β-lactams against MRSA and potentially other AMR pathogens

Choice in the context of informal care-giving

Extending choice and control for social care service users is a central feature of current English policies. However, these have comparatively little to say about choice in relation to the informal carers of relatives, friends or older people who are disabled or sick. To explore the realities of choice as experienced by carers, the present paper reviews research published in English since 1985 about three situations in which carers are likely to face choices: receiving social services; the entry of an older person to long-term care; and combining paid work and care. Thirteen electronic databases were searched, covering both the health and social care fields. Databases included: ASSIA; IBSS; Social Care Online; ISI Web of Knowledge; Medline; HMIC Sociological Abstracts; INGENTA; ZETOC; and the National Research Register. The search strategy combined terms that: (1) identified individuals with care-giving responsibilities; (2) identified people receiving help and support; and (3) described the process of interest (e.g. choice, decision-making and self-determination). The search identified comparatively few relevant studies, and so was supplemented by the findings from another recent review of empirical research on carers' choices about combining work and care. The research evidence suggests that carers' choices are shaped by two sets of factors: one relates to the nature of the care-giving relationship; and the second consists of wider organisational factors. A number of reasons may explain the invisibility of choice for carers in current policy proposals for increasing choice. In particular, it is suggested that underpinning conceptual models of the relationship between carers and formal service providers shape the extent to which carers can be offered choice and control on similar terms to service users. In particular, the exercise of choice by carers is likely to be highly problematic if it involves relinquishing some unpaid care-giving activities