Mid-Arm Point in PAEDiatrics (MAPPAED): An effective procedural aid for safe pleural decompression in trauma.

Objective: Life-threatening thoracic trauma requires emergency pleural decompression and thoracostomy and chest drain insertion are core trauma procedures. Reliably determining a safe site for pleural decompression in children can be challenging. We assessed whether the Mid-Arm Point (MAP) technique, a procedural aid proposed for use with injured adults, would also identify a safe site for pleural decompression in children.

Debriefing immediately after intubation in a children's emergency department is feasible and contributes to measurable improvements in patient safety.

Objective: In 2013, our intubations highlighted a safety gap - only 49% achieved first-pass success without hypoxia or hypotension. NAP4 recommended debriefing after intubation, but limited published methods existed. Primary aim is to implement a feasible process for immediate debriefing and feedback for emergency airway management.

A quality improvement initiative to increase the safety of pediatric emergency airway management.

Background: Emergency airway management is commonly associated with life-threatening hypoxia and hypotension which may be preventable.

Aims: The aim of this quality improvement study was to reduce the frequency of intubation-related hypoxia and hypotension.

Methods: This prospective quality improvement study was conducted over 4 years in the Emergency Department of The Royal Children's Hospital, Melbourne, Australia.

Proper-motion age dating of the progeny of Nova Scorpii AD 1437.

'Cataclysmic variables' are binary star systems in which one star of the pair is a white dwarf, and which often generate bright and energetic stellar outbursts. Classical novae are one type of outburst: when the white dwarf accretes enough matter from its companion, the resulting hydrogen-rich atmospheric envelope can host a runaway thermonuclear reaction that generates a rapid brightening. Achieving peak luminosities of up to one million times that of the Sun, all classical novae are recurrent, on timescales of months to millennia.

Implementation of NAP4 emergency airway management recommendations in a quaternary-level pediatric hospital.

Emergency airway management, particularly outside of the operating room, is associated with a high incidence of life-threatening adverse events. Based on the recommendations of the 4th National Audit Project, we aimed to develop hospital-wide systems changes to improve the safety of emergency airway management. We describe a framework for governance in the form of a hospital airway special interest group.

Planning for disasters involving children in Australia: A practical guide.

Children comprise 19% of the Australian population. Children are at risk of higher morbidity and mortality in disaster events than adults; however, there is a paucity of paediatric-specific disaster preparedness in Australia. Paediatric disaster plans should be developed, tested and renewed regularly.

A randomised controlled trial of cognitive aids for emergency airway equipment preparation in a Paediatric Emergency Department.

Background: Safety of emergency intubation may be improved by standardising equipment preparation; the efficacy of cognitive aids is unknown.

Methods: This randomised controlled trial compared no cognitive aid (control) with the use of a checklist or picture template for emergency airway equipment preparation in the Emergency Department of The Royal Children's Hospital, Melbourne.

Results: Sixty-three participants were recruited, 21 randomised to each group.

Laryngospasm With Apparent Aspiration During Sedation With Nitrous Oxide.

Nitrous oxide and oxygen mixture has become increasingly popular for the procedural sedation and analgesia of children in the emergency department. In general, nitrous oxide is regarded as a very safe agent according to large case series. We report a case of single-agent nitrous oxide sedation of a child, complicated by laryngospasm and radiographically confirmed bilateral upper lobe pulmonary opacities.

ERK2 drives tumour cell migration in three-dimensional microenvironments by suppressing expression of Rab17 and liprin-β2.

Upregulation of the extracellular signal-regulated kinase (ERK) pathway has been shown to contribute to tumour invasion and progression. Because the two predominant ERK isoforms (ERK1 and ERK2, also known as MAPK3 and MAPK1, respectively) are highly homologous and have indistinguishable kinase activities in vitro, both enzymes were believed to be redundant and interchangeable. To challenge this view, we show that ERK2 silencing inhibits invasive migration of MDA-MB-231 cells, and re-expression of ERK2 but not ERK1 restores the normal invasive phenotype.

Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration.

Inhibition of αvβ3 integrin or expression of oncogenic mutants of p53 promote invasive cell migration by enhancing endosomal recycling of α5β1 integrin under control of the Rab11 effector Rab-coupling protein (RCP). In this paper, we show that diacylglycerol kinase α (DGK-α), which phosphorylates diacylglycerol to phosphatidic acid (PA), was required for RCP to be mobilized to and tethered at the tips of invasive pseudopods and to allow RCP-dependent α5β1 recycling and the resulting invasiveness of tumor cells. Expression of a constitutive-active mutant of DGK-α drove RCP-dependent invasion in the absence of mutant p53 expression or αvβ3 inhibition, and conversely, an RCP mutant lacking the PA-binding C2 domain was not capable of being tethered at pseudopod tips.

Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression.

Here we show that Rab25 permits the sorting of ligand-occupied, active-conformation α5β1 integrin to late endosomes/lysosomes. Photoactivation and biochemical approaches show that lysosomally targeted integrins are not degraded but are retrogradely transported and recycled to the plasma membrane at the back of invading cells. This requires CLIC3, a protein upregulated in Rab25-expressing cells and tumors, which colocalizes with active α5β1 in late endosomes/lysosomes.

The mammalian MAPK/ERK pathway exhibits properties of a negative feedback amplifier.

Three-tiered kinase modules, such as the Raf-MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase)-ERK (extracellular signal-regulated kinase) mitogen-activated protein kinase pathway, are widespread in biology, suggesting that this structure conveys evolutionarily advantageous properties. We show that the three-tiered kinase amplifier module combined with negative feedback recapitulates the design principles of a negative feedback amplifier (NFA), which is used in electronic circuits to confer robustness, output stabilization, and linearization of nonlinear signal amplification. We used mathematical modeling and experimental validation to demonstrate that the ERK pathway has properties of an NFA that (i) converts intrinsic switch-like activation kinetics into graded linear responses, (ii) conveys robustness to changes in rates of reactions within the NFA module, and (iii) stabilizes outputs in response to drug-induced perturbations of the amplifier.

A relativistic type Ibc supernova without a detected gamma-ray burst.

Long duration gamma-ray bursts (GRBs) mark the explosive death of some massive stars and are a rare sub-class of type Ibc supernovae. They are distinguished by the production of an energetic and collimated relativistic outflow powered by a central engine (an accreting black hole or neutron star). Observationally, this outflow is manifested in the pulse of gamma-rays and a long-lived radio afterglow.

hnRNP A2 regulates alternative mRNA splicing of TP53INP2 to control invasive cell migration.

Largely owing to widespread deployment of microarray analysis, many of the transcriptional events associated with invasive cell migration are becoming clear. However, the transcriptional drives to invasive migration are likely modified by alternative splicing of pre-mRNAs to produce functionally distinct patterns of protein expression. Heterogenous nuclear ribonucleoprotein (hnRNP A2) is a known regulator of alternative splicing that is upregulated in a number of invasive cancer types.

Review article: Efficacy and safety of methoxyflurane analgesia in the emergency department and prehospital setting.

This article reviews the evidence for the analgesic efficacy of methoxyflurane in both prehospital and ED settings, as well as the adverse event profile associated with methoxyflurane use. Although there are no published controlled trials of methoxyflurane in sub-anaesthetic doses, available data indicate that it is an efficacious analgesic. There is inadequate evidence regarding its use as an agent for procedural pain.

Regulation of human myoblast differentiation by PEBP4.

The RAF-MEK-ERK pathway regulates both myoblast proliferation and differentiation; however, it is unclear how these events are coordinated. Here, we show that human phosphatidylethanolamine-binding protein 4 (PEBP4), a RAF kinase inhibitory protein (RKIP) family protein expressed preferentially in muscle, regulates the activity of the ERK pathway and myoblast differentiation by acting as a scaffold protein. In contrast to RKIP, which disrupts the RAF1-MEK interaction, PEBP4 forms ternary complexes with RAF1 and MEK, and can scaffold this interaction.

Phosphatase and feedback regulation of Raf-1 signaling.

The Raf-1 kinase is an effector of Ras GTPases that lies at the apex of the three-tier Raf/MEK/ERK pathway. Raf-1 activation is a complex process that entails two major events--relief of autoinhibition imposed by the regulatory domain and kinase domain activation. Recent studies indicate that the transition of Raf-1 from an active to an inactive state bears similar complexity to the activation process.

A Raf-1 mutant that dissociates MEK/extracellular signal-regulated kinase activation from malignant transformation and differentiation but not proliferation.

It is widely thought that the biological outcomes of Raf-1 activation are solely attributable to the activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. However, an increasing number of reports suggest that some Raf-1 functions are independent of this pathway. In this report we show that mutation of the amino-terminal 14-3-3 binding site of Raf-1 uncouples its ability to activate the MEK/ERK pathway from the induction of cell transformation and differentiation.