Defining abnormal slow EEG activity in acute ischaemic stroke: delta/alpha ratio as an optimal QEEG index

Objective: Quantitative electroencephalographic (QEEG) indices sensitive to abnormal slow (relative to faster) activity power seem uniquely informative for clinical management of ischaemic stroke (IS), including around acute reperfusion therapies. However these have not been compared between IS and control samples. The primary objective was to identify the QEEG slowing index and threshold value which can most accurately discriminate between IS patients and controls

Scale-free bursting in human cortex following hypoxia at birth

The human brain is fragile in the face of oxygen deprivation. Even a briefinterruption of metabolic supply at birth challenges an otherwise healthy neonatal cortex, leading to a cascade of homeostatic responses. During recovery from hypoxia, cortical activity exhibits a period of highly irregular electrical fluctuations known as burst suppression. Here we show that these bursts have fractal properties, with power-law scaling of burst sizes across a remarkable 5 orders of magnitude and a scale-free relationship between burst sizes and durations. Although burst waveforms vary greatly, their average shape converges to a simple form that is asymmetric at long time scales. Using a simple computational model, we argue that this asymmetry reflects activity-dependent changes in the excitatory-inhibitory balance of cortical neurons. Bursts become more symmetric following the resumption of normal activity, with a corresponding reorganization of burst scaling relationships. These findings place burst suppression in the broad class of scale-free physical processes termed crackling noise and suggest that the resumption of healthy activity reflects a fundamental reorganization in the relationship between neuronal activity and its underlying metabolic constraints

What stops hospital clinical staff from following protocols? An analysis of the incidence and factors behind the failure of bedside clinical staff to activate the rapid response system in a multi-campus Australian metropolitan healthcare service

OBJECTIVE: To explore the causes of failure to activate the rapid response system (RRS). The organisation has a recognised incidence of staff failing to act when confronted with a deteriorating patient and leading to adverse outcomes. DESIGN: A multi-method study using the following: a point prevalence survey to determine the incidence of abnormal simple bedside observations and activation of the rapid response team by clinical staff; a prospective audit of all patients experiencing a cardiac arrest, unplanned intensive care unit admission or death over an 8-week period; structured interviews of staff to explore cognitive and sociocultural barriers to activating the RRS. SETTING: Southern Health is a comprehensive healthcare network with 570 adult in-patient beds across four metropolitan teaching hospitals in the south-eastern sector of Melbourne. MEASUREMENTS: Frequency of physiological instability and outcomes within the in-patient hospital population. Qualitative data from staff interviews were thematically coded. RESULTS: The incidence of physiological instability in the acute adult population was 4.04%. Nearly half of these patients (42%) did not receive an appropriate clinical response from the staff, despite most (69.2%) recognising their patient met physiological criteria for activating the RRS, and being 'quite', or 'very' concerned about their patient (75.8%). Structured interviews with 91 staff members identified predominantly sociocultural reasons for failure to activate the RRS. CONCLUSIONS: Despite an organisational commitment to the RRS, clinical staff act on local cultural rules within the clinical environment that are usually not explicit. Better understanding of these informal rules may lead to more appropriate activation of the RRS

Novel features of early burst suppression predict outcome after birth asphyxia

Peer reviewe

An engineered cytidine deaminase for biocatalytic production of a key intermediate of the COVID-19 antiviral Molnupiravir

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What lies beneath? Reconstructing the primitive magmas fueling voluminous silicic volcanism using olivine-hosted melt inclusions

Understanding the origins of the mantle melts that drive voluminous silicic volcanism is challenging because primitive magmas are generally trapped at depth. The central Taupō Volcanic Zone (TVZ; New Zealand) hosts an extraordinarily productive region of rhyolitic caldera volcanism. Accompanying and interspersed with the rhyolitic products, there are traces of basalt to andesite preserved as enclaves or pyroclasts in caldera eruption products and occurring as small monogenetic eruptive centers between calderas. These mafic materials contain MgO-rich olivines (Fo79–86) that host melt inclusions capturing the most primitive basaltic melts fueling the central TVZ. Olivine-hosted melt inclusion compositions associated with the caldera volcanoes (intracaldera samples) contrast with those from the nearby, mafic intercaldera monogenetic centers. Intracaldera melt inclusions from the modern caldera volcanoes of Taupō and Okataina have lower abundances of incompatible elements, reflecting distinct mantle melts. There is a direct link showing that caldera-related silicic volcanism is fueled by basaltic magmas that have resulted from higher degrees of partial melting of a more depleted mantle source, along with distinct subduction signatures. The locations and vigor of Taupō and Okataina are fundamentally related to the degree of melting and flux of basalt from the mantle, and intercaldera mafic eruptive products are thus not representative of the feeder magmas for the caldera volcanoes. Inherited olivines and their melt inclusions provide a unique “window” into the mantle dynamics that drive the active TVZ silicic magmatic systems and may present a useful approach at other volcanoes that show evidence for mafic recharge

Synthesis of Stereoenriched Piperidines via Chemo- Enzymatic Dearomatization of Activated Pyridines

The development of efficient and sustainable methods for the synthesis of nitrogen heterocycles is an important goal for the chemical industry. In particular, substituted chiral piperidines are prominent targets due to their prevalence in medicinally relevant compounds and their precursors. A potential biocatalytic approach to the synthesis of this privileged scaffold would be the asymmetric dearomatization of readily assembled activated pyridines. However, nature has yet to yield a suitable biocatalyst specifically for this reaction. Here, by combining chemical synthesis and biocatalysis, we present a general chemo-enzymatic approach for the asymmetric dearomatization of activated pyridines for the preparation of substituted piperidines with precise stereochemistry. The key step involves a stereoselective one-pot amine oxidase/ene imine reductase cascade to convert N-substituted tetrahydropyridines to stereo-defined 3- and 3,4-substituted piperidines. This chemo-enzymatic approach has proved useful for key transformations in the syntheses of the antipsychotic drugs Preclamol and OSU-6162, as well as for the preparation of two important intermediates in synthetic routes of the ovarian cancer monotherapeutic Niraparib

Why don't hospital staff activate the rapid response system (RRS)? How frequently is it needed and can the process be improved?

Abstract Background The rapid response system (RRS) is a process of accessing help for health professionals when a patient under their care becomes severely ill. Recent studies and meta-analyses show a reduction in cardiac arrests by a one-third in hospitals that have introduced a rapid response team, although the effect on overall hospital mortality is less clear. It has been suggested that the difficulty in establishing the benefit of the RRS has been due to implementation difficulties and a reluctance of clinical staff to call for additional help. This assertion is supported by the observation that patients continue to have poor outcomes in our institution despite an established RRS being available. In many of these cases, the patient is often unstable for many hours or days without help being sought. These poor outcomes are often discovered in an ad hoc fashion, and the real numbers of patients who may benefit from the RRS is currently unknown. This study has been designed to answer three key questions to improve the RRS: estimate the scope of the problem in terms of numbers of patients requiring activation of the RRS; determine cognitive and socio-cultural barriers to calling the Rapid Response Team; and design and implement solutions to address the effectiveness of the RRS. Methods The extent of the problem will be addressed by establishing the incidence of patients who meet abnormal physiological criteria, as determined from a point prevalence investigation conducted across four hospitals. Follow-up review will determine if these patients subsequently require intensive care unit or critical care intervention. This study will be grounded in both cognitive and socio-cultural theoretical frameworks. The cognitive model of situation awareness will be used to determine psychological barriers to RRS activation, and socio-cultural models of interprofessional practice will be triangulated to inform further investigation. A multi-modal approach will be taken using reviews of clinical notes, structured interviews, and focus groups. Interventions will be designed using a human factors analysis approach. Ongoing surveillance of adverse outcomes and surveys of the safety climate in the clinical areas piloting the interventions will occur before and after implementation