Correlation of ICME Magnetic Fields at Radially Aligned Spacecraft.

The magnetic field structures of two interplanetary coronal mass ejections (ICMEs), each observed by a pair of spacecraft close to radial alignment, have been analysed. The ICMEs were observed in situ by MESSENGER and STEREO-B in November 2010 and November 2011, while the spacecraft were separated by more than 0.6 AU in heliocentric distance, less than 4° in heliographic longitude, and less than 7° in heliographic latitude. Both ICMEs took approximately two days to travel between the spacecraft. The ICME magnetic field profiles observed at MESSENGER have been mapped to the heliocentric distance of STEREO-B and compared directly to the profiles observed by STEREO-B. Figures that result from this mapping allow for easy qualitative assessment of similarity in the profiles. Macroscale features in the profiles that varied on timescales of one hour, and which corresponded to the underlying flux rope structure of the ICMEs, were well correlated in the solar east-west and north-south directed components, with Pearson's correlation coefficients of approximately 0.85 and 0.95, respectively; microscale features with timescales of one minute were uncorrelated. Overall correlation values in the profiles of one ICME were increased when an apparent change in the flux rope axis direction between the observing spacecraft was taken into account. The high degree of similarity seen in the magnetic field profiles may be interpreted in two ways. If the spacecraft sampled the same region of each ICME (i.e. if the spacecraft angular separations are neglected), the similarity indicates that there was little evolution in the underlying structure of the sampled region during propagation. Alternatively, if the spacecraft observed different, nearby regions within the ICMEs, it indicates that there was spatial homogeneity across those different regions. The field structure similarity observed in these ICMEs points to the value of placing in situ space weather monitors well upstream of the Earth.

Modeling observations of solar coronal mass ejections with heliospheric imagers verified with the Heliophysics System Observatory.

We present an advance toward accurately predicting the arrivals of coronal mass ejections (CMEs) at the terrestrial planets, including Earth. For the first time, we are able to assess a CME prediction model using data over two thirds of a solar cycle of observations with the Heliophysics System Observatory. We validate modeling results of 1337 CMEs observed with the Solar Terrestrial Relations Observatory (STEREO) heliospheric imagers (HI) (science data) from 8 years of observations by five in situ observing spacecraft. We use the self-similar expansion model for CME fronts assuming 60° longitudinal width, constant speed, and constant propagation direction. With these assumptions we find that 23%-35% of all CMEs that were predicted to hit a certain spacecraft lead to clear in situ signatures, so that for one correct prediction, two to three false alarms would have been issued. In addition, we find that the prediction accuracy does not degrade with the HI longitudinal separation from Earth. Predicted arrival times are on average within 2.6 ± 16.6 h difference of the in situ arrival time, similar to analytical and numerical modeling, and a true skill statistic of 0.21. We also discuss various factors that may improve the accuracy of space weather forecasting using wide-angle heliospheric imager observations. These results form a first-order approximated baseline of the prediction accuracy that is possible with HI and other methods used for data by an operational space weather mission at the Sun-Earth L5 point.

Monoaminergic agonists for acute traumatic brain injury.

BACKGROUND: Although there have been considerable gains in understanding the cascade of events that lead to secondary injury after traumatic brain injury (TBI), efforts to translate this understanding into new therapeutic, so-called neuroprotective approaches, have so far proven disappointing. As an alternative, there is growing interest in approaches to enhance brain repair after injury. Animal models suggest that agents enhancing monoaminergic (MA) transmission, particularly amphetamines, promote motor recovery from focal brain injury and it is proposed that this might represent a complementary means of therapeutic intervention in the later post-injury phase. OBJECTIVES: To evaluate the evidence that MAs improve final outcome after TBI. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library, Issue 2, 2005), the Cochrane Injuries Group's Specialised Register (to May 2005), MEDLINE (1966 to May 2005), EMBASE (1980 to May 2005) and the Science Citation Index (1992 to June 2005). We contacted researchers and authors of published and unpublished trials. Searches were updated in May 2005. SELECTION CRITERIA: Randomised controlled trials comparing the use of a MA (together with conventional non-pharmacological rehabilitative therapy) versus conventional non-pharmacological rehabilitative therapy alone. DATA COLLECTION AND ANALYSIS: Two authors independently screened records, extracted data and assessed trial quality. MAIN RESULTS: Although there is a limited clinical literature addressing this topic, none of the studies identified fully met inclusion criteria for this review. AUTHORS' CONCLUSIONS: At present there is insufficient evidence to support the routine use of MAs to promote recovery after TBI.

Participation of disabled children: how should it be characterised and measured?

PURPOSE: The aim of the paper is to explore the issues involved in measuring children's participation. METHOD: The concept of participation as encapsulated in the International Classification of Functioning, Disability and Health (ICF) is discussed as it applies to children. The essential components of any measure of children's participation are outlined, including participation essential for normal development and survival, leisure activities, and educational participation. Some existing instruments are briefly reviewed in terms of their coverage of the essential components and the adequacy of their approach to measurement. RESULTS: Key issues regarding the content of an adequate measure of participation include the need to consider the child's dependency on the family, and their changing abilities and autonomy as they grow older. Instruments may be most appropriate where they ask the child directly, implying use of visual as well as verbal presentation. Their focus should be on 'performance' such as whether and how often an activity is taken part in, and not incorporate degree of assistance within the measurement scaling. CONCLUSIONS: Currently available measures of children's participation all have some limitations in terms of their applicability across impairment groupings, whether the child can directly respond, and in the ICF components covered. The feasibility of developing measurement instruments of children's participation at different ages is discussed.

Severe head injury in children: emergency access to neurosurgery in the United Kingdom.

OBJECTIVE: To determine the scale of acute neurosurgery for severe traumatic brain injury (TBI) in childhood, and whether surgical evacuation for haematoma is achieved within four hours of presentation to an emergency department. METHODS: A 12 month audit of emergency access to all specialist neurosurgical and intensive care services in the UK. Severe TBI in a child was defined as that necessitating admission to intensive care. RESULTS: Of 448 children with severe head injuries, 91 (20.3%) underwent emergency neurosurgery, and 37% of these surgical patients had at least one non-reactive and dilated pupil. An acute subdural or epidural haematoma was present in 143/448 (31.9%) children, of whom 66 (46.2%) underwent surgery. Children needing surgical evacuation of haematoma were at a median distance of 29 km (interquartile range (IQR) 11.8-45.7) from their neurosurgical centre. One in four children took longer than one hour to reach hospital after injury. Once in an accident and emergency department, 41% took longer than fours hours to arrive at the regional centre. The median interval between time of accident and arrival at the surgical centre was 4.5 hours (IQR 2.23-7.73), and 79% of inter-hospital transfers were undertaken by the referring hospital rather than the regional centre. In cases where the regional centre undertook the transfer, none were completed within four hours of presentation-the median interval was 6.3 hours (IQR 5.1-8.12). CONCLUSIONS: The system of care for severely head injured children in the UK does not achieve surgical evacuation of a significant haematoma within four hours. The recommendation to use specialist regional paediatric transfer teams delays rather than expedites the emergency service.

Critical thresholds of intracranial pressure and cerebral perfusion pressure related to age in paediatric head injury.

BACKGROUND: The principal strategy for managing head injury is to reduce the frequency and severity of secondary brain insults from intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and hence improve outcome. Precise critical threshold levels have not been determined in head injured children. OBJECTIVE: To create a novel pressure-time index (PTI) measuring both duration and amplitude of insult, and then employ it to determine critical insult thresholds of ICP and CPP in children. METHODS: Prospective, observational, physiologically based study from Edinburgh and Newcastle, using patient monitored blood pressure, ICP, and CPP time series data. The PTI for ICP and CPP for 81 children, using theoretical values derived from physiological norms, was varied systematically to derive critical insult thresholds which delineate Glasgow outcome scale categories. RESULTS: The PTI for CPP had a very high predictive value for outcome (receiver operating characteristic analyses: area under curve = 0.957 and 0.890 for mortality and favourable outcome, respectively) and was more predictive than for ICP. Initial physiological values most accurately predicted favourable outcome. The CPP critical threshold values determined for children aged 2-6, 7-10, and 11-15 years were 48, 54, and 58 mm Hg. respectively. CONCLUSIONS: The PTI is the first substantive paediatric index of total ICP and CPP following head injury. The insult thresholds generated are identical to age related physiological values. Management guidelines for paediatric head injuries should take account of these CPP thresholds to titrate appropriate pressor therapy.

'Must try harder?': a family empowerment intervention for acquired brain injury.

This paper describes an intervention aimed at empowering parents of child survivors of acquired brain injury (ABI) in their interaction with teachers and other professionals involved in their child's education. The particular characteristics of the late morbidity of child ABI led to the design of an intervention in the form of a video and informational booklet that is the property of the family. Early response to the intervention has been extremely positive, although formal evaluation has been unexpectedly challenging.

Epidemiology of traumatic brain injury in children receiving intensive care in the UK.

AIMS: To describe the epidemiology of children with traumatic brain injury (TBI) admitted to paediatric intensive care units (PICUs) in the UK. METHODS: Prospective collection of clinical and demographic information from paediatric and adult intensive care units in the UK and Eire between February 2001 and August 2003. RESULTS: The UK prevalence rate for children (0-14 years) admitted to intensive care with TBI between February 2001 and August 2003 was 5.6 per 100,000 population per year (95% Poisson exact confidence intervals 5.17 to 6.05). Children admitted to PICUs with TBI were more deprived than the population as a whole (mean Townsend score for TBI admissions 1.19 v 0). The commonest mechanism of injury was a pedestrian accident (36%), most often occurring in children over 10. There was a significant summer peak in admissions in children under 10 years. Time of injury peaked in the late afternoon and early evening, a pattern that remained constant across the days of the week. Injuries involving motor vehicles have the highest mortality rates (23% of vehicle occupants, 12% of pedestrians) compared with cyclists (8%) and falls (3%). In two thirds of admissions (65%) TBI was an isolated injury. CONCLUSIONS: TBI in children requiring intensive care is more common in those from poorer backgrounds who have been involved in accidents as pedestrians. The summer peak in injury occurrence for 0-10 year olds and late afternoon timing give clear targets for community based injury prevention.

A case of infant botulism with a possible link to infant formula milk powder: evidence for the presence of more than one strain of Clostridium botulinum in clinical specimens and food.

Infant botulism was confirmed in a 5-month-old female by both isolation of Clostridium botulinum type B and by detection of type B botulinum neurotoxin in rectal washout and faeces. DNA fingerprinting of nine isolates from faeces yielded two different amplified-fragment length polymorphism (AFLP) patterns. C. botulinum was isolated from two of 14 food and drink items from the patient's home: C. botulinum type A was recovered from an opened container of dried rice pudding and C. botulinum type B from opened infant formula milk powder. Ten C. botulinum type B isolates from the opened infant formula yielded four AFLP patterns, two of which were indistinguishable from the clinical isolates. Fifteen unopened foods were tested and C. botulinum type B of a unique AFLP pattern was recovered from one unopened infant formula of the same batch as the opened container. It is suggested that multiple C. botulinum were present in both food and the intestine during infant botulism.

Visual impairment in children with acute nontraumatic coma.

PURPOSE: To determine the incidence and severity of visual impairment in children following acute nontraumatic coma. METHODS: An 18-month prospective epidemiologic study of acute nontraumatic coma was undertaken in the former Northern NHS Region of England. Children aged >1 month and <16 years were included in the study if they had a Glasgow Coma Score of < or = 12 for >6 hours or if they died within 6 hours of the onset of decreased levels of consciousness. For survivors, ophthalmologic assessments were performed 6 weeks and 12 months after presentation. RESULTS: Two hundred eighty-seven children were included in the study, of whom 127 died. Of the 137 examined survivors, 35 had visual abnormalities suspected by the examining neurologist during the ophthalmic assessment. Of these, visual impairment was confirmed in 10 children at the 6-week assessment by the pediatric ophthalmologist. At the 1 2-month assessment, visual impairment remained stable in 9 children and improved in 1. CONCLUSION: In this study, 6.6% of children surviving acute nontraumatic coma had visual impairment that persisted at the 12-month follow-up examination. Incidence of visual impairment in acute nontraumatic coma is 0.97 per 100,000 children per year.

Incidence, aetiology, and outcome of non-traumatic coma: a population based study.

AIM: To determine the incidence, presentation, aetiology, and outcome of non-traumatic coma in children aged between 1 month and 16 years. METHODS: In this prospective, population based, epidemiological study in the former Northern NHS region of the UK, cases were notified following any hospital admission or community death associated with non-traumatic coma. Coma was defined as a Glasgow Coma Score below 12 for more than six hours. RESULTS: The incidence of non-traumatic coma was 30.8 per 100 000 children under 16 per year (6.0 per 100 000 general population per year). The age specific incidence was notably higher in the first year of life (160 per 100 000 children per year). CNS specific presentations became commoner with increasing age. In infants, nearly two thirds of presentations were with non-specific, systemic signs. Infection was the commonest overall aetiology. Aetiology remained unknown in 14% despite extensive investigation and/or autopsy. Mortality was highly dependent on aetiology, with aetiology specific mortality rates varying from 3% to 84%. With follow up to approximately 12 months, overall series mortality was 46%.

Cognitive and adaptive outcomes and age at insult effects after non-traumatic coma.

Cognitive and adaptive behavioural outcome were studied in the identified survivors of a population based study of non-traumatic coma (NTC) in childhood. Children were assessed early (six weeks) and late (12 months) after NTC. At least 7% of those children in whom no suspicions of prior neurodevelopmental morbidity existed showed moderate or severe disability following NTC. Children over 2 years of age at insult showed some improvement between early and late assessments; however, children below 2 years showed no improvement. Differing age at insult effects were observed between aetiological groups. A relation between early age at first insult and poor outcome was particularly evident among children experiencing NTC caused by epilepsy.

Compatibility of tirofiban HCl with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride during simulated Y-site administration.

OBJECTIVE: To study the compatibility of tirofiban HCl injection 0-05 mg/ml with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride infusion solutions during simulated Y-site administration. METHOD: Tirofiban HCl, dopamine HCl, famotidine, lidocaine HCl and potassium chloride infusions were each prepared from their respective concentrates as per current clinical preparation instructions in both 0.9% sodium chloride and 5% dextrose solutions at both the minimum and maximum concentrations normally administered. Sodium heparin premixed infusion solutions in 5% dextrose and 0-45% sodium chloride were used as-is. Tirofiban HCl solutions were combined 1:1 (simulated Y-site administration) with the dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride solutions in separate glass containers and polyvinylchloride Y-site infusion lines. Samples were held for 4 h at room temperature under ambient fluorescent light and were assayed for changes in drug content, degradation, pH, appearance and turbidity. Activity of sodium heparin solutions was measured using an aPTT coagulation assay. RESULTS: All mixtures remained clear and colourless with no visual indication of instability, i.e. precipitation. Clarity of solutions was confirmed by turbidometric analysis. There was no significant loss of drug, increase in known degradates, or appearance of unknown drug-related peaks as determined by HPLC. The activity of heparin in heparin-containing solutions remained unchanged. The pH of all test-solutions remained constant. CONCLUSION: Tirofiban HCl injection 0.05 mg/ml can be co-infused by Y-site administration with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride injection solutions.

Solid-phase extraction and liquid chromatographic quantitation of the antiarrhythmic drug L-768673 in a microemulsion formulation.

A sensitive and specific method based in solid-phase extraction and reverse-phase liquid chromatography was developed and validated for the quantitation of L-768673 in a microemulsion formulation. Following a water wash, the drug was eluted from the extraction column with acetonitrile and was analyzed on a reverse-phase C18 column with UV detection at 245 nm. The mobile phase consisted of acetonitrile-0.2% trifluoroacetic acid, 0.1% triethylamine (53:47 v/v). The retention time L-768673 was approximately 28 min with a flow rate of 1.5 ml min-1.

The mechanisms controlling physiologically stimulated changes in rat brain glucose and lactate: a microdialysis study.

1. This study is concerned with the supply of metabolic substrates for neuronal metabolism. Experiments were carried out to investigate whether mechanisms demonstrated in cultured astrocytes also occurred in vivo; these were cAMP-mediated breakdown of glycogen and glutamate uptake-stimulated release of lactate. 2. In vivo microdialysis was used in freely moving rats. Lactate and glucose in the dialysate were assayed using enzyme-based on-line assays. Drugs were given locally through the dialysis probe. Regional cerebral blood flow was measured using the hydrogen clearance method. 3. There was an increase in dialysate glucose in response to the beta-adrenoceptor agonist isoprenaline and to 8-bromo-cAMP, an analogue of cAMP, the second messenger of beta-adrenoceptor stimulation. The effect of isoprenaline was blocked by the antagonist propranolol. Isoprenaline had no effect on dialysate lactate, which was increased by the glutamate uptake blocker beta-D,L-threohydroxyaspartate (THA). 4. Physiological stimulation of neuronal activity produced an increase in both lactate and glucose. The increase in lactate was depressed in the presence of THA but was unaffected by propranolol. The increase in glucose was blocked by propranolol. Regional cerebral blood flow was increased by physiological stimulation but was unaffected by propranolol. 5. These results demonstrate that physiologically stimulated increases in glucose and lactate in the brain are mediated by different mechanisms.

Astrocytes and the delivery of glucose from plasma to neurons.

Conventional kinetic models of brain glucose uptake and metabolism that visualize brain glucose as being in a single pool in equilibrium with plasma, are unable to account for some recently described experimental findings. These include microdialysis demonstrations of a brain extracellular fluid glucose concentration that is both low, and significantly affected by changes in neuronal activity; and observations of transient glucose export (transient negative whole-brain arteriovenous differences) in certain neuro-intensive care settings. A kinetic model that treats brain glucose as divided into more than one, kinetically distinct, compartment, implying the presence of a glucose "reservoir" behind the blood-brain barrier, and with plasma glucose initially entering a compartment other than the brain extracellular fluid, is more consistent with these experimental observations. Neuroanatomical considerations suggest that plasma glucose may initially exchange with an intracellular astrocytic glucose pool, rather than the brain extracellular fluid. Astrocyte glycogen, mobilized at times of increased neuronal activity, could form the reservoir whose presence is inferred from demonstrations of transient glucose export, but only if glycogenolytic products can be exported from astrocytes as glucose. This hypothesis is considered in the light of the frequently suggested concept of a "nutritional" role for perivascular astrocytes and invertebrate glia, taking up blood-borne glucose and passing on metabolic substrates to neurons. The implications of this model for 2-deoxyglucose-based methods for regional cerebral metabolic rate estimation are discussed. In general, errors due to the approximations inherent in the conventional three compartment kinetic model, may be expected to become less significant as metabolism is averaged over space and time. Thus the three-compartment model is probably acceptable for the description of metabolism at the relatively low spatial and temporal resolution of these techniques.

Dephosphorylation of 2-deoxyglucose 6-phosphate and 2-deoxyglucose export from cultured astrocytes.

Neurotransmitter-stimulated mobilization of astrocyte glycogen has been proposed as a basis for local energy homeostasis in brain. However, uncertainty remains over the fate of astrocyte glycogen. Upon transfer of cultured astrocytes pre-loaded with [2-3H]2-deoxyglucose 6-phosphate at non-tracer concentrations to a glucose-free, 2-deoxyglucose-free medium, rapid dephosphorylation of a proportion of the intracellular 2-deoxyglucose 6-phosphate pool and export of 2-deoxyglucose to the extracellular fluid occurs. Astrocytes show very low, basal rates of gluconeogenesis from pyruvate (approx. 1 nmol mg protein-1 h-1). Astrocytes in vivo may be capable of physiologically significant glucose export from glucose-6-phosphate. The low gluconeogenic activity in astrocytes suggests that the most likely source of glucose-6-phosphate may be glycogen. These findings support the hypothesis that export, as glucose, to adjacent neurons may be one of the possible fate(s) of astrocytic glycogen. Such export of glycogen as glucose occurring in response to increases in neuronal activity could contribute to energy homeostasis on a paracrine scale within brain.

The heliospheric magnetic field over the South polar region of the sun.

Magnetic field measurements from the Ulysses space mission overthe south polar regions of the sun showed that the structure and properties of the three-dimensional heliosphere were determined by the fast solar wind flow and magnetic fields from the large coronal holes in the polar regions of the sun. This conclusion applies at the current, minimum phase of the 11-year solar activity cycle. Unexpectedly, the radial component of the magnetic field was independent of latitude. The high-latitude magnetic field deviated significantly from the expected Parker geometry, probably because of large amplitude transverse fluctuations. Low-frequency fluctuations had a high level of variance. The rate of occurrence of discontinuities also increased significantly at high latitudes.