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Substantial new information is presented on upper Artinskian–Kungurian deposits in Timor-Leste and in the Canning, Southern Carnarvon and northern Perth basins of Western Australia. These basins, situated between about 35°S and 55°S palaeolatitude, formed part of the East Gondwana interior rift, a precursor to the rift that 100 my later formed the Indian Ocean in this region. Timor lay near the main axis of the East Gondwana interior rift, whereas the Western Australian basins were marginal splays from the rift axis. The main depocentres developed as a result of faulting that was initiated during the Late Pennsylvanian. Detailed lithostratigraphic and biostratigraphic analyses have been made on the newly recognized Bua-bai limestone and the type Cribas Group in Timor, the Noonkanbah Formation in the Canning Basin, the Byro Group in the Merlinleigh Sub-basin of the Southern Carnarvon Basin, and the Carynginia Formation in the northern Perth Basin. In Timor the succession, which is highly disrupted by faulting, was deposited under open-marine conditions probably in a shelf–basin setting. Restricted, very shallow-water seas flooded the Canning Basin and the Merlinleigh–Byro–Irwin sub-basins of the Southern Carnarvon and northern Perth basins and had highly variable oxygen levels and salinities typical of estuarine environments. A similar pattern of warming and bathymetric change is recognized in all studied basins. During the early part of the late Artinskian cool conditions prevailed, with water temperatures 0–4 °C forming sea ice in the Merlinleigh–Byro–Irwin rift. Rapid warming during the latter part of the late Artinskian was accompanied by maximum marine flooding close to the Artinskian–Kungurian boundary. Climatic and bathymetric conditions then allowed carbonate mounds, with larger fusulines and a variety of algae, to develop in the northern part of the rift system, and Tubiphytes, conodonts, and brachiopods with Tethyan affinities to migrate into the marginal-rift basins despite the generally adverse water quality at these depositional sites. Comparison between the stratigraphic record from the East Gondwana interior rift and coeval records from Lhasa and Sibumasu indicate a similar pattern of climate change during the Carboniferous to end Cisuralian. Similar trends probably are present in Eastern Australia although there is confusion over the correlation of some units.

A new terrestrial–marine assemblage from the lower beds of a thin outcrop section of the Kockatea Shale in the northern Perth Basin, Western Australia, contains a range of fossil groups, most of which are rare or poorly known from the Lower Triassic of the region. To date, the collection includes spinose acritarchs, organic-cemented agglutinated foraminifera, lingulids, minute bivalves and gastropods, ammonoids, spinicaudatans, insects, austriocaridid crustaceans, actinopterygians, a temnospondyl-like mandible, plant remains, and spores and pollen. Of these groups, the insects, crustaceans and macroplant remains are recorded for the first time from this unit. Palynomorphs permit correlation to nearby sections where conodonts indicate an early Olenekian (Smithian) age. The locality likely represents the margin of an Early Triassic shallow interior sea with variable estuarine-like water conditions, at the southwestern end of an elongate embayment within the East Gondwana interior rift–sag system preserved along the Western Australian margin. Monospecific spinose acritarch assemblages intertwined with amorphous organic matter may represent phytoplankton blooms that accumulated as mats, and suggest potentially eutrophic surface waters. The assemblage represents a mixure of marine and terrestrial taxa, suggesting variations in water conditions or that fresh/brackish-water and terrestrial organisms were transported from adjacent biotopes. Some of the lower dark shaly beds are dominated by spinicaudatans, likely indicating periods when the depositional water body was ephemeral, isolated, or subjected to other difficult environmental conditions. The biota of the Kockatea Shale is insufficiently known to estimate biotic diversity and relationships of individual taxa to their Permian progenitors and Triassic successors, but provides a glimpse into a coastal-zone from the interior of eastern Gondwana. Specialist collecting is needed to clarify the taxonomy of many groups, and comparisons to other Lower Triassic sites are required to provide insights into the pattern of biotic decline and recovery at the end-Permian crisis.

We tested the hypothesis that induction of neuronal NO synthase (nNOS) impairs vascular smooth muscle contractility after hypoxia. nNOS protein was increased in aorta, mesenteric arterioles, pulmonary arteries, brain, and diaphragm from rats exposed to 8% O2 for 48 hours and in human aortic SMCs after hypoxic incubation (1% O2). Ca2+-dependent NO synthase activity was increased in endothelium-denuded aortic segments from hypoxia-exposed rats. NG-nitro-L-arginine methyl ester enhanced the contractile responses of endothelium-denuded aortic rings and mesenteric arterioles from hypoxia-exposed but not normoxic rats (P < 0.05). The hypoxia-inducible mRNA transcript expressed by human cells was found to contain a novel 5′-untranslated region, consistent with activation of transcription in the genomic region contiguous with exon 2. Translational efficiency of this transcript is markedly increased compared with previously described human nNOS mRNAs. Transgenic mice possessing a lacZ reporter construct under control of these genomic sequences demonstrated expression of the construct after exposure to hypoxia (8% O2, 48 hours) in the aorta, mesenteric arterioles, renal papilla, and brain. These results reveal a novel human nNOS promoter that confers the ability to rapidly upregulate nNOS expression in response to hypoxia with a functionally significant effect on vascular smooth muscle contraction.

Expression of the neuronal nitric-oxide synthase (nNOS) mRNA is subject to complex cell-specific transcriptional regulation, which is mediated by alternative promoters. Unexpectedly, we identified a 89-nucleotide alternatively spliced exon located in the 5'-untranslated region between exon 1 variants and a common exon 2 that contains the translational initiation codon. Alternative splicing events that do not affect the open reading frame are distinctly uncommon in mammals; therefore, we assessed its functional relevance. Transient transfection of reporter RNAs performed in a variety of cell types revealed that this alternatively spliced exon acts as a potent translational repressor. Stably transfected cell lines confirmed that the alternatively spliced exon inhibited translation of the native nNOS open reading frame. Reverse transcription-PCR and RNase protection assays indicated that nNOS mRNAs containing this exon are common and expressed in both a promoter-specific and tissue-restricted fashion. Mutational analysis identified the functional cis-element within this novel exon, and a secondary structure prediction revealed that it forms a putative stem-loop. RNA electrophoretic mobility shift assay techniques revealed that a specific cytoplasmic RNA-binding complex interacts with this motif. Hence, a unique splicing event within a 5'-untranslated region is demonstrated to introduce a translational control element. This represents a newer model for the translational control of a mammalian mRNA.

We compared the potency and duration of action of rocuronium in Chinese and Caucasian patients during general anesthesia. Thirty-six women (18 Caucasian and 18 Chinese) and 36 children (18 Caucasian and 18 Chinese) were evaluated during the administration of propofol/fentanyl anesthesia. Patients in each age group were randomized into three subgroups to receive single doses of 0.06, 0. 12, or 0.18 mg/kg rocuronium (adults) or 0.12, 0.18, or 0.24 mg/kg rocuronium (children). Neuromuscular blockade was assessed by electromyography of the adductor pollicis after train-of-four (TOF) stimulation of the ulnar nerve. Dose response curves were constructed when maximum neuromuscular depression of the first twitch of the train (T(1)) was obtained. A second bolus dose of rocuronium was then administered to a total dose of 0.6 mg/kg. The times of spontaneous recovery to T(1) 10%, 25%, and 90% of control and to TOF 0.25, 0.50, and 0.70 were recorded. For both adults and children, recovery occurred later in Chinese than in Caucasian patients (P

UNLABELLED We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. IMPLICATIONS These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.

The effects of thermal maturation upon the abundance and composition of the tricyclic terpanes have been investigated within a single sedimentary horizon within the Dun Caan Shale Member (Isle of Skye, Scotland) intruded by a 0.9 m thick Tertiary dolerite dyke. Heating by the igneous body caused the concentrations of all 13β(H),14α(H) and 13α(H),14α(H) tricyclic terpanes to increase towards or within the effective ‘oil window’, recording generation from abundant non-hydrocarbon precursors, such as kerogen- and asphaltene-bound components. Progressive changes in tricyclic terpane composition accompany these concentration changes. An increase in the C23 βα/αα maturity parameter towards the dyke resulted from the relatively greater rate of generation of the βα isomer, combined with the earlier decline in concentration (by degradation or isomerisation) of the αα component. The tricyclics/(tricyclics+hopanes) parameter shows a dramatic increase within the latter part of the oil window, due to the greater relative thermal stability of the tricyclic terpanes. The quantitative data demonstrate the importance of the processes of generation (from non-hydrocarbon fractions of the sedimentary organic matter) and thermal degradation in the operation of tricyclic terpane maturity parameters.

The purpose of this study was to compare the mivacurium infusion requirements and neuromuscular recovery in adults and children during propofol/opioid and sevoflurane anesthesia. Seventy-five adult and 75 pediatric patients were randomized to receive propofol/opioid 0.5 or 1.0 minimum alveolar anesthetic concentration (MAC) (age-related) sevoflurane anesthesia. Plasma cholinesterase (PChE) activity was measured. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation every 10 s and adductor pollicis electromyography. A bolus of 2 x the 95% effective dose of mivacurium (0.25 mg/kg) was followed by an infusion titrated to maintain 90%-95% blockade. Mivacurium doses were recorded every 5 min. At the end of surgery, the infusion was stopped, and recovery from mivacurium was monitored until TOFor =0.7. PChE concentrations were within the normal range (adults 4-12 KU/L, children 6-16 KU/L) and correlated with mivacurium dose. Mivacurium infusion rates were higher in children than in adults: at 30 min, the rates in children were 13.1 +/- 6.4, 8.1 +/- 4.7, and 5.2 +/- 2.9 microg x kg(-1) x min(-1) at 0, 0.5, and 1.0 MAC sevoflurane, respectively; the corresponding rates in adults were 5.9 +/- 3.1, 4.3 +/- 1.7, and 2.9 +/- 0.7 microg x kg(-1) x min(-1) (P0.01). Sevoflurane decreased mivacurium requirements, maximal decreases at 45 min in children and 10 min in adults, and delayed neuromuscular function recovery. Children recovered twice as quickly as adults, achieving TOFor =0.7 at 9.8 +/- 2.5, 11.4 +/- 2.8, and 19.6 +/- 6.3 min compared with 19.9 +/- 5.4, 26.4 +/- 8.3, and 32.9 +/- 9.8 min in adults (P0.0001). In conclusion, mivacurium requirements were correlated with PChE, were greater in children than in adults, and were reduced by sevoflurane. Neuromuscular recovery occurred more rapidly in children and was delayed by sevoflurane.The mivacurium infusion requirement to maintain constant 90%-95% neuromuscular block during anesthesia is correlated with plasma cholinesterase activity. It is increased in children and reduced by the inhaled anesthetic sevoflurane. Despite the larger dose administered to children, recovery from block occurred more rapidly in children than in adults and was delayed by sevoflurane.

The solvation equation [ Eq. (1) ] can be applied to reversed-phase HPLC capacity factors (i.e. log SP=log k). (1) log SP =c+rR 2 +sπ H 2 +a Σ α H 2 +b Σ β H 2 +vV x S. SP is a solute property (e.g., solubility or partition coefficient) and the explanatory variables are solute descriptors as follows: R2 is an excess molar refraction, π2H is the solute dipolarity/dipolarisability, Σα2H and Σβ2H are the solute overall or effective hydrogen-bond acidity and basicity, and Vx is the McGowan characteristic volume and c, r, s, a, b and v are constants that are characteristic of the particular mobile/stationary phase combination. Only a limited hydrophobicity range can be covered using log k values obtained by isocratic chromatography at a fixed mobile phase composition. Gradient elution is more versatile and 29 compounds were examined under 20 different reversed-phase HPLC conditions using automated fast gradient methods. Using Eq. (1) with gradient retention time (tRg) in place of log SP an excellent correlation was obtained with the solute descriptors. This provides an experimental demonstration that gradient retention times (tRg) can be treated as linear free-energy related parameters just like log k or log P values. Because gradient retention times cannot be used for inter-laboratory comparisons, they were scaled by conversion to chromatographic hydrophobicity index (CHI) values by correlation with data from a calibration set of compounds with known CHI values. By comparing the coefficients r, s, a, b and v of Eq. (1) as determined from different chromatographic systems, the relative effects of different solute properties can be revealed and thus the selectivity of HPLC columns can be predicted. It is also possible to compare chromatographic behaviour with that of other partition systems, such as octanol–water, cyclohexane–water and blood–brain barrier distributions.

We give a full account of our extensive measurements of vortex mutual friction in rotating superfluid 3He, in both the A- and B-phases. The B-phase results are in qualitative agreement with a theory based on the concept of "spectral flow"; the agreement becomes quantitative if an effective energy gap of 0.63Δ is used, but the justification for such a substitution is not clear. The vortex core transition, at first not seen because of metastability and hysteresis, has now been observed. Detailed investigation suggests that the high temperature vortex state is a temperature dependent mixture of at least two vortex types. The A-phase mutual friction is found to be well described by two hydrodynamic coefficients, the orbital viscosity and the orbital inertia. The latter corresponds to an orbital angular momentum per Cooper pair of (0.0015 ± 0.0017) ℏ, consistent with the prediction of the spectral flow theory. We find that the most uniform l texture is obtained by cooling through Tc while rotating, and then stopping rotation. Detailed investigation of textural memory effects shows that the uniform l-up and l-down textures are associated with opposite directions of rotation. We discuss the various types of texture that may be formed in our experiments. Finally, we compare our mutual friction results with those found in 4HeII.

Midazolam has GABAergic effects in children that may modify propofol-induced involuntary movements, yet delay recovery. In a double-blind, randomized study, 24 children (2-7 yr of age, ASA physical status I or II) undergoing short surgical procedures received midazolam 0.5 mg/kg (Group M) or placebo (Group P) per os 20-30 min before propofol anesthesia (5 mg/kg intravenously followed by an infusion). Blind observers scored sedation and anxiety levels (scale 1-4) before premedication, at separation from parents, and at induction of anesthesia. Induction and emergence were videotaped, and body movements were recorded. During recovery, times to eye opening and maximum Steward (SS = 6) and Vancouver Sedative Recovery (VSRS = 22) scores were noted. Parents were questioned about side effects that may have occurred during the following week. Both groups were similar in age, sex, weight, timing of premedication, propofol dose, and duration of surgery. The incidence of involuntary movements did not differ between groups but was higher at induction (79%) than on emergence (25%) (P < 0.05). Anxiety and sedation scores were similar in Group P and Group M, but recovery took longer after midazolam, with eye opening (mean +/- SD) 24 +/- 7 vs 43 +/- 18 min, maximum SS (median and range) 27 (13-37) vs 55 (24-138) min, and maximum VSRS 51 (30-100) vs 80 (50-130) min. Children returned to normal activity in 1 (0-5) day, and none exhibited neurological complications. We conclude that an oral premedicant dose of midazolam prolongs recovery from anesthesia in children without affecting dystonic movements after propofol.

Pregnant CD-1 mice (30 per group) and female New Zealand White rabbits (15 per group) were exposed by inhalation to 0, 1000, 4000 and 8000 ppm methyl tertiary-butyl ether (MTBE) vapor for 6 h a day during gestational days (GD) 6-15 and 6-18, respectively. Maternal body weights, clinical observations and food consumption were recorded throughout gestation for both species. At scheduled euthanization (GD 18 for mice and GD 29 for rabbits), fetuses were weighed, sexed and examined for external, visceral (including craniofacial) and skeletal alterations. For both species, the pregnancy rate was high and equivalent across all groups; no pregnant animals died or aborted. There were no does that delivered early, but there were three mouse dams in the control group and two dams in the 4000 ppm group that delivered early and were removed from the study. In mice, maternal body weights, body weight gain, corrected maternal gestational weight change and food consumption were significantly reduced in mice at 8000 ppm. Hypoactivity and ataxia were observed in dams exposed to 4000 and 8000 ppm. Gestational parameters affected at 8000 ppm included post-implantation loss (due to increased late resorptions and dead fetuses) and altered sex ratio (decreased males); fetal body weights per litter were reduced at 4000 and 8000 ppm. There was a significantly increased incidence of cleft palate at 8000 ppm; this resulted in increased incidences of pooled external and visceral malformations and of total malformations at this exposure concentration. There were also treatment-related increases in the incidence of individual skeletal variations at 4000 and 8000 ppm. In rabbits, maternal weight gain and food consumption were significantly reduced at 4000 and 8000 ppm. Relative liver weights were also reduced at 8000 ppm. All gestational parameters were equivalent across all groups, including pre- and post-implantation loss, fetal sex ratios, litter size and fetal weights/litter. There was no evidence of treatment-related teratogenicity observed at any dose tested in rabbits. The no-observed-effect levels (NOELs) for maternal and developmental toxicity were both 1000 ppm in mice and 1000 ppm and at least 8000 ppm, respectively, in rabbits.

The Universe contains much more matter than antimatter, which is probably the result of processes in the early Universe in which baryon number was not conserved. These processes may have occurred during the electroweak phase transition, when elementary particles first acquired mass. It is impossible to study directly processes relevant to the early Universe, because of the extreme energies involved. One is therefore forced to investigate laboratory systems with analogous phase transitions. Much of the behavior of superfluid 3He is analogous to that predicted within the standard model of the electroweak interaction. Superfluids and liquid crystals have already been used to investigate cosmic-string production; here we describe experiments on 3He that demonstrate the creation of excitation momentum (which we call momentogenesis) by quantized vortices in the superfluid. The underlying physics of this process is similar to that associated with the creation of baryons within cosmic strings, and our results provide quantitative support for this type of baryogenesis.

We have measured the resistive and reactive mutual friction coefficients in rotating superfluid ${}^{3}\mathrm{H}\mathrm{e}\ensuremath{-}A$ at $29.3\mathrm{bars}$ pressure. The results agree with those predicted from the equation of orbital hydrodynamics for two quantum continuous vortices if the previously measured value of the orbital viscosity is used. Our results put an upper limit on the orbital inertia of less than $0.005\ensuremath{\Elzxh}$ per Cooper pair. We explain our observation of history-dependent textures by noting that the ease of formation of continuous vortices depends on the relative direction of $\mathbf{l}$ and the rotation axis.

The thermal effects of an igneous intrusion (0.9 m thick dyke) upon the abundance and composition of hopanes and hopenes are reported for a suite of samples within a single sedimentary horizon (a carbonate concretion > 1.6 m in diameter) from the Jurassic Dun Caan Shale Member (Bearreraig Bay, Isle of Skye, Scotland). The conventional hopane maturity parameters show normal trends towards the dyke and through the “oil window” (approximately 22–45 cm from the dyke, i.e. 25–50% dyke thickness), with the exception of the Ts (Ts + Tm) parameter which shows a progressive fall with increasing maturity, until the middle of the oil window when it increases markedly. Molecular abundances demonstrate that the observed changes in the hopane maturity parameters result from the combined effects of generation (presumed to be from kerogen) and degradation of individual compounds, with isomerization in the free phase being minimal or unimportant. The unexpected behaviour of Ts (Ts + Tm) results from the minimal generation of Ts compared with Tm. Our data indicate that the Ts skeleton is not present in the kerogen, and at least under the elevated heating associated with an igneous intrusion may be derived from 18α(H)-22,29,30-trisnorneohop-13(18)-ene in the bitumen. Thermally induced modifications to hopane carbon number distributions are also reported, and show that oil-source rock correlations between samples of different maturity must consider the effects of generation/degradation of kerogen-bound hopanes.

This study was conducted to evaluate the subchronic toxicity of 4-vinylcyclohexene (VCH). Male and female Sprague–Dawley rats and B6C3F 1 mice were exposed by inhalation to VCH 6 hr/day, 5 days/week for 13 weeks. Rats were exposed to 0, 250, 1000, or 1500 ppm, and mice were exposed to 0, 50, 250, or 1000 ppm. In addition, another group of rats and mice was exposed to 1000 ppm butadiene so that a comparison could be made between the two compounds. Exposure to 1000 ppm VCH resulted in deaths of all male mice and 5/10 female mice on Test Days 11 or 12. Three additional female mice exposed to 1000 ppm VCH died prior to study completion. The most notable compound-related clinical sign was lethargy observed in the 1500 ppm VCH-exposed rats and 1000 ppm VCH-exposed mice. Male rats exposed to 1500 ppm VCH had significantly lower body weights compared to controls, and male and female rats in the 1500 ppm group had significantly lower body weight gains. None of the VCH-exposed animals or butadiene-exposed rats showed any compound-related hematological effects. However, mice exposed to 1000 ppm butadiene exhibited mild macrocytic anemia. Clinical chemistry evaluation and urinalysis showed no compound-related effects in rats exposed to either VCH or butadiene. Male and female rats exposed to 1000 or 1500 ppm VCH or 1000 ppm butadiene had increased absolute and/or relative liver weights, and male rats in these same exposure groups had increased relative kidney weights. Microscopically, increased accumulation of hyaline droplets was observed in the kidneys of male rats from all VCH exposure groups. Although compound-related, the droplets were not accompanied by cytotoxicity. In mice, the most notable adverse histopathological effect was ovarian atrophy in females exposed to 1000 ppm VCH or 1000 ppm butadiene. The atrophy was slightly more severe in the VCH-exposed females than in the butadiene-exposed females. There were no other compound-related pathological effects in male or female mice exposed to VCH. Additionally, butadiene-exposed male mice had decreased testicular weights, accompanied by slight testicular degeneration and atrophy. For VCH exposure, the no-observed-adverse-effect-level is 1000 ppm for rats based on lethargy and lowered body weights and 250 ppm for mice based on mortality and ovarian atrophy.

Background The rapid recovery from mivacurium- induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit. Methods In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg x kg(-1) edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode. Results Children arrived in the postanesthesia care unit 8.2 +/- 3-4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/- 0.05 vs. 0.93 +/- 0.01, P0.7 in all children. Adults arrived in the postanesthesia care unit 12.9 +/- 5.3 min after reversal of neuromuscular block(P Conclusions This study demonstrated that, in adults, failure to reverse mivacurium neuromuscular block was associated with an increased incidence of residual block. Such weakness was not observed in children receiving similar anesthetic and neuromuscular blocking regimens.

Currently, most elective pediatric surgery is performed on an out-patient basis. The objective of this case-control study was to identify potential determinants of patient cancellation at a children's hospital. Cases were defined as patients that were canceled on the day of surgery, whereas controls were those patients who underwent surgery on the scheduled date. Demographic and clinical data were collected using chart review. Approximately 10% of all day surgery patients were canceled on the day scheduled for surgery, half for reasons deemed preventable. Of the preventable cancellations, stepwise logistic regression analysis showed that patients attending only the surgeon's office prior to day surgery, were more likely to be canceled because of inadequate preparation, compared to those patients attending both the surgeon's office and the hospital preoperative clinic (adjusted odds ratio = 3.18; 95% CI: 1.32, 7.63).

Aims Neonatal attendances to Children’s Emergency Departments (CED) are an increasing issue, with jaundice a common presenting problem. Assessment of the level of jaundice has traditionally been by a blood test. This not only has the disadvantages of distress, inconvenience and cost, but also exposes neonates to a busy CED for prolonged time periods. Would the introduction of a simple transcutaneous bilirubinometer into the department safely and accurately improve the delivery of our care? Methods All neonates who presented to our CED between 17/09/15 and 18/11/15 requiring investigation for jaundice had both a transcutaneous bilirubinometer (three readings taken on the sternum) and a laboratory analysis of serum bilirubin. We compared results obtained from both measurements, determined what proportion of babies could avoid a blood test (in accordance with NICE guidance on the use of transcutaneous bilirubinometers) and whether blood results changed management. The study is ongoing. Results Figure 1 19 babies presented with jaundice (two were excluded as no serum bilirubin results were available). Babies ranged from gestational ages of 36 to 41 weeks, presenting age range 1 to 28 days. 7 of these were for jaundice alone, referred from community midwives. 12 presented with both jaundice and another complaint e.g. weight loss, poor feeding. On average, the bilirubinometer result was within 12% of the serum bilirubin (mean = 12%, range 1%–30%). 12/17 (71%) had transcutaneous bilirubin readings below 250 nmol/L. In one case only, serum results changed management – initiating phototherapy. However, given transcutaneous levels were above 250nmol/L, in line with NICE guidelines, blood tests would have been initiated regardless. 3/12 (25%) were admitted immediately following high readings, improving patient flow and efficiency. Conclusion In our initial population, up to 71% of babies could have avoided the need for blood tests, offered simple advice and feeding support. Furthermore, if a community transcutaneous bilirubinometer had been available, potentially 24% of these attendances at CED could have been avoided altogether. When used in line with NICE guidance, the transcutaneous bilirubinometer is an easy to use, safe, non-invasive and accurate method of measuring jaundice in a neonate.

Introduction Major trauma is the leading cause of death and disability in children, however compared to adults, children represent a much smaller number. The Trauma Audit and Research Network (TARN) states that 65.8% of Paediatric Major Trauma does not initially present to a Children’s Major Trauma Centre (MTC), however there is little research into the role of a Paediatric Trauma Unit (PTU) in the management of paediatric major trauma (PMT). Aim To review all admitted paediatric trauma patients at a PTU, focussing on the management of PMT, to establish whether the PTU management of these patients was safe and comparable to recommended practice. Methods A retrospective review of all trauma patients age

Aims To evaluate the safeguarding assessment of “Under 2s” presenting to a Children’s Emergency Department (CED) with suspected skull fracture. Methods A retrospective study between the 1st January 2012 to 1st January 2015 for children under 2 years old who underwent radiological investigation (CT or XRAY Head) for acute head injury. Results 52 patients underwent investigation (CT head/skull x-ray) the average age was 6 months. Of these development was assessed in 40% of cases and a full body examination was documented in 67%. 22 (42%) had confirmed skull fractures (SF), with an average age of 7 months (4.6–9.5 months). Most fractures (78%) were simple, linear and parietal. 21/22 cases (95%) presented with localised head swelling, bruising or haematoma and the most common mechanisms were: fall 74%, unexplained 13% and accidentally dropped 9%. 65% were discussed with social services. 10/22 (45%) underwent skeletal survey (SS), with additional fractures (rib fractures) detected in 1 child.12/22 did not have a SS of whom half were under 6 months age. Overall 7/52 (13%) were on social service plans at time of presentation. All children who underwent skeletal survey had a strategy meeting. Only 2/52 (4%) cases were defined as definitive NAI, only one had a skull fracture. All skull fractures were admitted. 2 children were transferred to neurosurgical centres for close observation (small subdural bleed) neither were defined as NAI. Conclusion It was interesting to note the small number of SS performed in the less than 6 months age group, which on notes review appeared to be attributed to the clinicians assessment of low likelihood of NAI in that individual patient. From this limited study the presence of a skull fracture did not help predict the likelihood of NAI. The diagnosis of NAI relies on a multiagency approach; there is no gold-standard for diagnosis. This is the first UK study looking at this population of children. There is no validated decision making tool for this population of children with skull fractures to aid inclusion/exclusion of non-accidental injury. A multicentre study would allow larger numbers to draw conclusions with regards to decision making.

This chapter reviews both linear and branched monohydric aliphatic C1 to C6 alcohols. The C7 to C20 monohydric alcohols are covered in Chapter 78. The low molecular weight alcohols, including methanol, ethanol, 1-propanol, and isopropanol are used extensively in industry (16). These alcohols exist as volatile liquids at ambient temperatures, and exposure can occur in both industrial and nonindustrial environments. This review discusses primarily dermal and inhalation routes of exposure, which are the major routes of occupational exposure to alcohols. Many of the high-production alcohols such as methanol, ethanol, propanols, and butanols cause adverse effects when ingested; ingestion, however, is not a major route of occupational exposure. There are some alcohols that have produced adverse effects in humans, including death, in an occupational environment. Nevertheless, alcohols have been used extensively in the workplace generally with few or minor problems. Occasionally, methanol, ethanol, and the propanols produce a skin sensitizing response in humans. In some, but not all, cases the sensitization response was considered to be due to contaminants and not to the alcohol itself. A common property of some of the alcohols is to produce local irritation to the skin, eyes, and respiratory tract, and the effect or potency varies for the type of alcohol. Many alcohols produce minimal or no adverse effects in humans, possibly because of low exposure combined with the low toxicity potential of the alcohol. Few alcohols produce neuropathic effects in humans. Abuse of products containing methanol and ethanol has produced some indications of neurotoxicity in humans, but nothing has been reported in an occupational environment. 2-Hexanol produces neurotoxicity by the oral and intraperitoneal routes in animals, but there is no evidence of such an effect having occurred in the workplace. There is no clear evidence that occupational exposures to alcohols represent a carcinogenic risk to humans. Based on epidemiological data, there is an association between the manufacture of ethanol and isopropanol by the strong acid process (a process no longer used in the United States) and an excess of upper respiratory tract cancer in humans. The effect has been attributed to by-products such as dialkyl sulfates and sulfuric acid, not the alcohols themselves. Some of these alcohols such as ethanol and isopropanol can enhance the toxic effects of various chemicals, particularly hepatotoxins. It is thought that the effects may be due largely to an inductive effect of the alcohol on microsomal enzymes, particularly the cytochrome P450 system, which may allow a greater metabolic conversion of the hepatotoxin to its toxic metabolite. Keywords: Methanol; Inhalation studies; Ethanol; 1-Propanol; Isopropanol; Butanols; Amyl alcohols; Hexanols

BACKGROUND--Sepiolite is an absorbent clay that is used as pet litter. It forms thin crystals, which are a transition between chain and layered silicates. Inhalation studies in animals have shown no evidence of pulmonary damage. This paper reports a cross sectional study of the total work force of the largest sepiolite production plant in the world. METHODS--Two hundred and eighteen workers (210 men and eight women) were studied. Height, age, and smoking history were recorded. Chest radiographs were read according to the International Labour Office (ILO) classification by two readers. Readings were used to construct a numerical score, which was then used in statistical analyses. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were divided by the square of the height. Casella size selective personal samplers were used in randomly selected operatives to collect dust eight years before the rest of the study was carried out. These samples were evaluated gravimetrically. Total dust samples were examined by optical and electron microscopes. Results were analysed by bivariate linear regression, chi 2 tests, and analysis of variance. RESULTS--When allowance was made for smoking habit workers exposed to dry dust showed a significantly greater decline in FEV1 with age than workers with little exposure to dry dust. A similar pattern applied to FVC. Radiographic score showed deterioration with age but no clear differences from other variables. High concentrations of dust were found in the bagging department and also in the classifier shed. CONCLUSIONS--The major finding was that lung function deteriorated more rapidly in those who had had more exposure to dust, but there was no evidence of any accompanying radiographic change.

Aim To implement an effective pathway to improve the central line service offered by our hospital – a service improvement project led by a Paediatric and Anaesthetic trainee. Background Central lines (CI) are required for a variety of paediatric patients and are referred from almost every department in our hospital; and from other hospitals within our region. An recent adverse incident lead to suboptimal care for a child and illustrated major inefficiencies in our referral system. This led us to review the process of central line placement at our centre – where currently no formal pathway exists. Methods Firstly we performed a retrospective audit over a year to ascertain our current workload (1 st May 2012 and 31 st May 2013.) Data was collected from coding regarding insertion of CI. Secondly a multidisciplinary team was formed of the individual departments involved in the placement of CI. We involved senior staff who could enable and implement the reforms necessary. Results A total of 118 CI lines were inserted. In 70% (83) it was the primary (only) procedure of these 73% (61) were medical 10% (8) were trauma and orthopaedics 6% (5) were surgical 5% (4) were respiratory 2% (2) were oncology 2% (2) ENT and 1% (1) for cardiology and 30% (35) as the non-primary procedure. Implementation This data has been used to bring forward a costed business case for a dedicated central line service. This has involved A Scoping exercise for all equipment and resources requirements Establishing the training requirements needed for the team placing CI’s Liaison with the relevant departments to establish their requirements and to create a communications network. Immediate instigation of a pilot pathway in consultation with managers and our multidisciplinary team. To improve the referral pathway, efficiency and management of the patient. Also documentation and care of central lines post insertion. Conclusion This piece of work shows how trainees can influence the systems they work within leading to real change. It demonstrates how communication and collaboration across disciplines can improve not only the patient care, but improve efficiency and reduce cost.

A novel protocol is described for obtaining preliminary data on repeated dose systemic effects and reproductive/developmental toxicity. The test protocol was developed by a group of experts at the request of the U.S. Environmental Protection Agency (EPA) for use as part of a Screening Information Data Set on high production volume chemicals. Interest in this protocol is shared by several regulatory agencies, including the Organization for Economic Cooperation, the European Community, and the EPA. To validate the study protocol, ethylene glycol monomethyl ether (EGME) was used. After a dosing period of approximately 6 weeks, EGME showed both systemic and reproductive/developmental effects similar to those previously reported using standard protocols. Thus, this test protocol may be used as a screening tool for high production volume chemicals.

formed, written consent for inclusion in randomized controlled clinical trials, the use of their medical re cords in case reports/series, or for quality assurance and medical audit studies. In 2001, a review of 1,189 publications in six lead ing anesthesia journals found documented ethics com mittee approval in 71%, and individual written consent in 66% of the articles. rates varied among the journals with the highest rates (94% and 87%) for prospective clinical trials, and the lowest (2% and 3%) for case reports/series. Observational studies, prospective and retrospective, ranked in between. 1 Shortly after these results were published, most countries introduced leg islation to protect the privacy of individuals and pre

We have studied the effect of prior administration of non-depolarizing neuromuscular blocking drugs on suxamethonium-induced increases in masseter muscle tension in 21 children aged 3-10 yr, anaesthetized with nitrous oxide and halothane using supramaximal stimulation of the ulnar nerve and the nerve to masseter. Resting tension and isometric force of contraction were measured in the adductor pollicis and masseter muscles. A sub-paralysing dose of tubocurarine 0.05 mg kg-1, a paralysing dose of atracurium 0.5 mg kg-1 or saline was given, followed 3 min later by suxamethonium 1 mg kg-1. Onset times of suxamethonium and atracurium block were shorter in the masseter than in the adductor pollicis muscle. When preceded by a sub-paralysing dose of tubocurarine, suxamethonium produced an increase in masseter tension (47 (SEM 15) g) similar to that produced by suxamethonium alone (59 (13) g). Prior administration of a paralysing dose of atracurium almost abolished this increase in tension (2.5 (2.5) g) (P less than 0.05 vs saline). The tension increase in adductor pollicis was 0, 3.2 (2.2) and 5.9 (1.1) g in the atracurium, tubocurarine and saline groups, respectively. Tubocurarine and atracurium prevented muscle fasciculations in all patients. It was concluded that increased muscle tone is a normal response to suxamethonium and is greater in the masseter than adductor pollicis. Sub-paralysing doses of non-depolarizing neuromuscular blockers have little effect, in contrast with paralysing doses. This suggests that the effect is mediated via postsynaptic receptors.

This study was performed to determine the effects of various doses of succinylcholine on resting tension and evoked twitch height at the masseter and adductor pollicis muscles in children. Twenty patients, aged 3–10yr, ASA physical status I or II, were randomly assigned to receive succinylcholine 0.15, 0.25, 0.50 or 1.00 mg · kg−1, during halothane-nitrous oxide anaesthesia. Supramaximal train-of-four stimulation was applied simultaneously to the ulnar nerve and the nerve to the masseter. Transducers recorded force at the jaw and the thumb. Maximum blockade of the first twitch (T1) and maximum resting tension change were measured. Potency of succinylcholine at the two muscles was estimated by linear regression of the logit transformation of T1 versus log dose. The relationship between resting tension change and log dose was established by linear regression. The masseter muscle was more sensitive to succinylcholine than the adductor pollicis with an ED95 of 0.28 ± 0.02 (mean ±SEM) vs 0.44 ± 0.05 mg · kg−1 (P < 0.05). Onset of neuromuscular blockade was faster at the masseter, and recovery occurred simultaneously in both muscles. A dose-related increase in resting tension was observed in both muscles, but its magnitude was five times greater at the masseter. With succinylcholine, 1 mg · kg−1, this increase was 51.6 ± 16.8 g at the masseter and 9.1 ± 2.3 g at the adductor pollicis. Tension returned to baseline within 1–2 min. It is concluded that in children (1) succinylcholine produces dose-related changes in resting tension; (2) this effect, although quantitatively important at the masseter, is not restricted to that muscle; and (3) relatively small doses of succinylcholine are required to block neuromuscular transmission at the jaw.

The sensitivity of the masseter to atracurium was measured in ten children aged 3–10 yr undergoing elective surgery, and compared with that of the adductor pollicis. During nitrous oxide-halothane anaesthesia and mechanical ventilation, supramaximal nerve stimulation was applied to the ulnar nerve at the elbow and to the nerve to the masseter, at a point inferior to the zygomatic arch, anterior to the mandibular condyle. Jaw closure was measured by a force displacement transducer system attached to an oral airway and connected to a metal frame fixed to the operating table 10 cm caudad to the chin. Cumulative dose—response curves for atracurium were obtained by the injection of doses followed by an infusion to compensate for elimination. The mean ED5Os and ED95s were similar at the masseter and the adductor pollicis. At the masseter, these were 0.150 ±0.013, mean ±SEM, mg · kg−1 and 0.254 ±0.021 mg · kg−1, respectively. At the adductor pollicis, corresponding values were 0.145 ±0.009 mg · kg−1, and 0.259 ±0.016 mg · kg−1. However, this relationship was not constant in every patient, and in some patients the masseter was much more sensitive than the adductor pollicis. The time from injection of the first dose of atracurium to maximum blockade was 2.5 ±0.2 min at the masseter and 3.2 ±0.2 min at the adductor pollicis (P < 0.05). It is concluded that when atracurium is administered to paediatric patients, neuromuscular blockade is usually of the same intensity at each muscle but occurs sooner at the masseter than at the adductor pollicis. However, because of the large interpatient variability, return of adductor pollicis function may not imply complete masseter muscle recovery.

The increases in tension at the masseter and adductor pollicis muscles following succinylcholine, 1 mg · kg−1, during halothane anaesthesia were measured in eight children, 3–10 yr, with strabismus. The results were compared with those obtained in a control group of general surgical patients. Supramaximal train-of-four (TOF) stimulation was applied to the ulnar nerve and the nerve to the masseter simultaneously. Jaw closure was measured by a force transducer system. In all patients, succinylcholine caused an increase in resting tone at the jaw and at the thumb. In the strabismus group, the magnitude of this increase was 55.7 ±23.2 g, mean ±SD, at the jaw and 11.3 ±5.6 g at the thumb. This was not significantly different from the values obtained in controls, 45.3 ±33.4 g and 7.9 ±4.2 g, respectively. The duration of the phenomenon was 1–2 min in both muscles studied, and was not statistically different in the strabismus group. Time to complete neuromuscular blockade was significantly faster at the masseter, 31 ±6 sec —control groups; 39 ±11 sec —strabismus group, than at adductor pollicis, 61 ±34 sec —control groups; 75 ±28 sec —strabismus group (P < 0.05 and 0.013 respectively). It is concluded that succinylcholine causes similar increases in jaw tension and comparable degrees of neuromuscular blockade in patients undergoing strabismus surgery as in other children.

Purpose of review This review will examine research ethics in the context of globalization of clinical trials and recent rapid developments in bioscience. It will focus on international ethical guidelines and the functions of research ethics review boards in research governance. Consent issues in genetic research, which must comply with privacy laws by protecting confidentiality and privacy of personal health data, will be discussed. Recent findings There has been a rapid expansion of genomic and proteonomic research and biotechnology in the last decade. International ethical guidelines have been updated and the bioscience industry has developed ethics policies. At the same time, problems in academic anesthesia in the US and UK have been identified, leading to recommendations to train physician-scientists in anesthesia to stimulate research activity in the future. Anesthesiologists are joining interdisciplinary research teams and the concept of evidence-based translational research is emerging. Summary Anesthesiologists are moving towards participation in interdisciplinary research teams. They are well placed to speed the translation of research discovery into clinical practice and provide evidence-based perioperative care. This review provides the ethical framework that anesthesiologists will need to meet the challenges of this changing pattern of practice.