The effect of dexmedetomidine on postoperative behaviour change in children: a randomised controlled trial.

Children may develop changes in their behaviour following general anaesthesia. Some examples of negative behaviour include temper tantrums and nightmares, as well as sleep and eating disorders. The aim of this study was to determine whether dexmedetomidine reduces the incidence of negative behaviour change after anaesthesia for day case surgery in children aged two to seven years. Children were randomly allocated to one of three groups: a premedication group received 2 mg.kg-1 intranasal dexmedetomidine; an intra-operative group received 1 mg.kg-1 intravenous dexmedetomidine; and a control group. The primary outcome was the incidence of negative behaviour on postoperative day 3 using the Post-Hospitalisation Behaviour Questionnaire for Ambulatory Surgery (PHBQ-AS) and the Strength and Difficulties Questionnaire (SDQ). Secondary outcomes included: the incidence of negative behaviour on postoperative days 14 and 28; anxiety at induction; emergence delirium; pain; length of recovery and hospital stay; and any adverse events. The data for 247 patients were analysed. Negative behaviour change on postoperative day 3 was similar between all three groups when measured with the PHBQ-AS (47%, 44% and 51% respectively; adjusted p=0.99) and the SDQ (median scores 7.5, 6.0 and 8.0 respectively; adjusted p=0.99). The incidence of negative behaviour in the group who received dexmedetomidine intra-operatively was less at postoperative day 28 (15% compared with 36% in the dexmedetomidine premedication group and 41% in the control group, p<0.001). We conclude that dexmedetomidine does not reduce the incidence of negative behaviour on postoperative day 3 in two to seven-year olds having day case procedures.

Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) in children: a randomized controlled trial.

BACKGROUND: Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) was introduced to adult anaesthesia to improve the safety of airway management during apnoea before intubation. The objective of our study was to determine whether THRIVE safely prolongs apnoeic oxygenation in children. METHODS: This was a randomized controlled trial in 48 healthy children, with normal airways and cardiorespiratory function, in age groups 0-6 and 7-24 months, 2-5 and 6-10 yr old, presenting for elective surgery or imaging under general anaesthesia. All children were induced with sevoflurane, O2, and N2O, followed by muscle relaxation with rocuronium, and standardized preoxygenation with bag-and-mask ventilation. The control arm received jaw support during apnoea, whereas the THRIVE arm received jaw support during apnoea and age-specific flow rates. The primary outcome was to demonstrate that children allocated to THRIVE maintain transcutaneous haemoglobin saturation at least twice as long as the expected age-dependent apnoea time in the control group. RESULTS: Both study arms (each n=24) were similar in age and weight. The apnoea time was significantly shorter in the control arm: average 109.2 (95% CI 28.8) s in the control arm and 192 s in the THRIVE arm (0-6 months), 147.3 (95% CI 18.9) and 237 s (7-24 months), 190.5 (95% CI 15.3) and 320 s (2-5 yr), and 260.8 (95% CI 37.5) and 430 s (6-10 yr), respectively. Average transcutaneous haemoglobin saturation remained at 99.6% (95% CI 0.2) during THRIVE. Transcutaneous CO2 increased to a similar extent in both arms, with 2.4 (95% CI 0.5) mm Hg min-1 for the control arm and 2.4 (95% CI 0.4) mm Hg min-1 for the THRIVE arm. CONCLUSION: Transnasal humidified rapid-insufflation ventilatory exchange prolongs the safe apnoea time in healthy children but has no effect to improve CO2 clearance. CLINICAL TRIAL REGISTRATION: ACTRN12615001319561.

Organic molecules in the Sheepbed Mudstone, Gale Crater, Mars.

The Sample Analysis at Mars (SAM) instrument on board the Mars Science Laboratory Curiosity rover is designed to conduct inorganic and organic chemical analyses of the atmosphere and the surface regolith and rocks to help evaluate the past and present habitability potential of Mars at Gale Crater. Central to this task is the development of an inventory of any organic molecules present to elucidate processes associated with their origin, diagenesis, concentration, and long-term preservation. This will guide the future search for biosignatures. Here we report the definitive identification of chlorobenzene (150-300 parts per billion by weight (ppbw)) and C2 to C4 dichloroalkanes (up to 70 ppbw) with the SAM gas chromatograph mass spectrometer (GCMS) and detection of chlorobenzene in the direct evolved gas analysis (EGA) mode, in multiple portions of the fines from the Cumberland drill hole in the Sheepbed mudstone at Yellowknife Bay. When combined with GCMS and EGA data from multiple scooped and drilled samples, blank runs, and supporting laboratory analog studies, the elevated levels of chlorobenzene and the dichloroalkanes cannot be solely explained by instrument background sources known to be present in SAM. We conclude that these chlorinated hydrocarbons are the reaction products of Martian chlorine and organic carbon derived from Martian sources (e.g., igneous, hydrothermal, atmospheric, or biological) or exogenous sources such as meteorites, comets, or interplanetary dust particles. KEY POINTS: First in situ evidence of nonterrestrial organics in Martian surface sediments Chlorinated hydrocarbons identified in the Sheepbed mudstone by SAM Organics preserved in sample exposed to ionizing radiation and oxidative condition.

Evidence for indigenous nitrogen in sedimentary and aeolian deposits from the Curiosity rover investigations at Gale crater, Mars.

The Sample Analysis at Mars (SAM) investigation on the Mars Science Laboratory (MSL) Curiosity rover has detected oxidized nitrogen-bearing compounds during pyrolysis of scooped aeolian sediments and drilled sedimentary deposits within Gale crater. Total N concentrations ranged from 20 to 250 nmol N per sample. After subtraction of known N sources in SAM, our results support the equivalent of 110-300 ppm of nitrate in the Rocknest (RN) aeolian samples, and 70-260 and 330-1,100 ppm nitrate in John Klein (JK) and Cumberland (CB) mudstone deposits, respectively. Discovery of indigenous martian nitrogen in Mars surface materials has important implications for habitability and, specifically, for the potential evolution of a nitrogen cycle at some point in martian history. The detection of nitrate in both wind-drifted fines (RN) and in mudstone (JK, CB) is likely a result of N2 fixation to nitrate generated by thermal shock from impact or volcanic plume lightning on ancient Mars. Fixed nitrogen could have facilitated the development of a primitive nitrogen cycle on the surface of ancient Mars, potentially providing a biochemically accessible source of nitrogen.

Mars atmosphere. Mars methane detection and variability at Gale crater.

Reports of plumes or patches of methane in the martian atmosphere that vary over monthly time scales have defied explanation to date. From in situ measurements made over a 20-month period by the tunable laser spectrometer of the Sample Analysis at Mars instrument suite on Curiosity at Gale crater, we report detection of background levels of atmospheric methane of mean value 0.69 ± 0.25 parts per billion by volume (ppbv) at the 95% confidence interval (CI). This abundance is lower than model estimates of ultraviolet degradation of accreted interplanetary dust particles or carbonaceous chondrite material. Additionally, in four sequential measurements spanning a 60-sol period (where 1 sol is a martian day), we observed elevated levels of methane of 7.2 ± 2.1 ppbv (95% CI), implying that Mars is episodically producing methane from an additional unknown source.

Volatile and organic compositions of sedimentary rocks in Yellowknife Bay, Gale crater, Mars.

H2O, CO2, SO2, O2, H2, H2S, HCl, chlorinated hydrocarbons, NO, and other trace gases were evolved during pyrolysis of two mudstone samples acquired by the Curiosity rover at Yellowknife Bay within Gale crater, Mars. H2O/OH-bearing phases included 2:1 phyllosilicate(s), bassanite, akaganeite, and amorphous materials. Thermal decomposition of carbonates and combustion of organic materials are candidate sources for the CO2. Concurrent evolution of O2 and chlorinated hydrocarbons suggests the presence of oxychlorine phase(s). Sulfides are likely sources for sulfur-bearing species. Higher abundances of chlorinated hydrocarbons in the mudstone compared with Rocknest windblown materials previously analyzed by Curiosity suggest that indigenous martian or meteoritic organic carbon sources may be preserved in the mudstone; however, the carbon source for the chlorinated hydrocarbons is not definitively of martian origin.

Volatile, isotope, and organic analysis of martian fines with the Mars Curiosity rover.

Samples from the Rocknest aeolian deposit were heated to ~835°C under helium flow and evolved gases analyzed by Curiosity's Sample Analysis at Mars instrument suite. H2O, SO2, CO2, and O2 were the major gases released. Water abundance (1.5 to 3 weight percent) and release temperature suggest that H2O is bound within an amorphous component of the sample. Decomposition of fine-grained Fe or Mg carbonate is the likely source of much of the evolved CO2. Evolved O2 is coincident with the release of Cl, suggesting that oxygen is produced from thermal decomposition of an oxychloride compound. Elevated δD values are consistent with recent atmospheric exchange. Carbon isotopes indicate multiple carbon sources in the fines. Several simple organic compounds were detected, but they are not definitively martian in origin.

The association between time to disposition plan in the emergency department and in-hospital mortality of general medical patients.

BACKGROUND: A perceived risk of time-limited emergency department (ED) assessment of patients is inadequate workup leading to inappropriate disposition. The aim of this study was to examine the association of time to disposition plan (TDP) on ED length of stay (LOS) and correlate this to mortality. METHODS: A retrospective review of data collected from ED information systems at three hospitals was conducted between June 2008 and October 2009. Included patients were admitted to a general medical unit. Patients were excluded if admitted to intensive care, coronary care, a cardiac monitored bed or required surgery in first 24 h or had an expected LOS of <48 h. Multivariate regression analysis was used to identify independent associations with mortality. RESULTS: A total of 10,107 patient episodes was analysed, of which 6768 patients (67.0%) had an ED LOS of ≥8 h. There was significant effect modification by ED LOS in the association of TDP and mortality. In the setting of longer ED LOS, a TDP of <4 h was associated with significantly higher mortality (OR 1.57, 95% CI: 1.28-1.92, P < 0.001), corrected for age, gender and triage category. This association was not significant when ED LOS was <8 h (OR 0.88, 95% CI: 0.60-1.27, P = 0.49). CONCLUSIONS: In the setting of prolonged ED LOS, completing ED assessment and management within 4 h of presentation was associated with significantly higher mortality. Further prospective studies are required to understand the relationship between rapid decision making in the ED and patient safety.

Probing the material properties and phase transitions of ferroelectric liquid crystals by determination of the Landau potential.

The full Landau potential of several, widely varying ferroelectric liquid-crystalline materials has been experimentally determined. Tilt angle and polarisation data is analysed across the SmA to SmC transition for varying applied electric-field amplitudes, allowing the determination of all the coefficients of the generalised Landau model of ferroelectric liquid crystals. The materials investigated encompass different materials, including low-polarisation mixtures to high-polarisation single-component materials. The materials also possess a variation in the order of the SmA to SmC phase transition from strongly first order to strongly second order. The effects of both the polarisation and order of phase transition of the system are discussed with respect to the various terms of the generalised Landau model. Further, the mechanisms behind the difference between a first- and second-order phase transition are discussed with respect to the Landau potential and the second Landau coefficient b .

Quantitative experimental determination of the Landau-potential of chiral enantiomer doped ferroelectric liquid crystals.

The full Landau potential was determined for a ferroelectric liquid crystal doped with varying concentrations of the chiral dopant R1011 and its enantiomer S1011. A multi-curve fitting procedure using temperature and electric field dependent tilt angle and polarization data was employed to the generalized Landau model of ferroelectric liquid crystals. From this analysis the three Landau coefficients as well as the polarization-tilt coupling parameters were obtained as a function of dopant concentration and configuration. It is shown that the two most varied parameters are those of the first Landau coefficient alpha and the (chiral) linear polarization-tilt coupling constant C. The effect on the first Landau term is equivalent for the two dopants of opposite handedness indicating its achiral nature, while the effect on the (chiral) bilinear coupling term differs for the R1011 and S1011 dopant, increasing and decreasing the coupling between tilt and polarization respectively. This difference in the bilinear coupling term quantifiably evidences that the R1011 dopant increases and S1011 dopant reduces the inherent chirality in this system.

Experimental determination of the full Landau potential of bent-core doped ferroelectric liquid crystals.

The full Landau potential of a ferroelectric liquid crystal, doped with two different bent-core molecules at varying concentration, was determined experimentally. Using a multicurve fitting procedure, temperature and electric field dependent tilt angle and polarization measurements were analyzed according to the generalized Landau model of ferroelectric liquid crystals. From this analysis the three Landau coefficients as well as the polarization-tilt coupling parameters were obtained as a function of dopant concentration. It is shown that the two most varied parameters are those of the first Landau coefficient and the (chiral) linear polarization-tilt coupling constant. The results quantitatively verify the chiral induction capability of nonchiral bent-core shaped dopants and an observed increase in the electroclinic effect with increasing dopant concentration.

Measurement of cardiac troponin I levels in the emergency department: predictive value for cardiac and all-cause mortality.

OBJECTIVE: To assess the predictive value of cardiac troponin I levels in cardiac and all-cause mortality in patients presenting to an emergency department. DESIGN: A prospective cohort study. SETTING: The emergency department of a major tertiary teaching hospital in metropolitan Melbourne over a six-week period in 1998. PATIENTS: All patients with requests for cardiac enzyme level measurement. MAIN OUTCOME MEASURES: Cardiac and all-cause mortality within 30 days of presentation. RESULTS: 424 patients (232 men, 192 women; age range, 16-93 years) were reviewed. The 30-day mortality rate was 7.3% (31/424); in patients with raised levels of both creatine kinase (CK)-MB isoenzyme and troponin I this rate was 27% (7/26; 95% CI, 13%-44%); and in those with troponin I levels above 2 microg/L, but normal CK-MB values, it was 24% (5/21; 95% CI, 5%-43%). The mortality rate in the group with normal results of cardiac markers was 4.3% (14/328; 95% CI, 2.1%-6.5%). Patients with minor increases in troponin I levels (minimal myocardial damage) showed an intermediate 30-day mortality rate (13%, 5/39; 95% CI, 2%-24%). Other predictors of 30-day mortality included age, presentation with shortness of breath, and electrocardiography (ECG) changes diagnostic of acute myocardial infarction or consistent with ischaemia. Cardiovascular causes were responsible for most of the deaths in patients with raised troponin I levels. Multivariate logistic regression analysis showed that raised levels of troponin (> 2.0 microg/L), but not of CK-MB, predict 30-day mortality rate. CONCLUSIONS: Compared with CK-MB, cardiac troponin I more accurately predicts 30-day mortality rates in patients presenting to the emergency department. Moreover, troponin I levels identify additional groups of patients at increased risk of death not so identified by measuring CK-MB values.

Induction of labour: a comparison of two methods with particular concern to patient acceptability.

Induction of labour is a common obstetric intervention. When the cervix is unfavourable ripening agents are used, commonly prostaglandin E2. There are several methods of administration of prostaglandin E2 and little comparative work has been performed as to their acceptability by patients. Patients undergoing induction of labour by prostaglandin E2 were randomised to receive either intravaginal gel or an intravaginal slow-release pessary. Patient satisfaction with the method received was then assessed. Sixty-nine patients were randomised, 34 to receive gel and 35 to receive a pessary. Median scores for satisfaction of the induction process were the same for both methods; however, satisfaction with the labour was increased with those who had been randomised to the pessary group (median pessary=5, gel=4). There may be a marginal improvement in patient satisfaction when a slow-release intravaginal prostaglandin E2 pessary is used for the induction of labour.

The twilight of national sovereignty.

The institution envisaged in the Moscow Declaration, refined in the Atlantic Charter, and elaborated at Dunbarton Oaks, was called 'the United Nations'. The Preamble to its Charter began with the words 'We the peoples', and Articles 3 and 4 provided that its members should be states. The underlying assumption appeared to be that the words 'nation', 'people' and 'state' were interchangeable. To challenge that assumption may appear to be playing at word games, equivalent to doing the Times crossword. But since language is the vehicle by which we formulate and communicate our thinking, words have always been invested with a power, and certainly a life, of their own. Words have legal consequences. If the word 'A' is synonymous with 'B', then all the rights and obligations pertaining to an 'A' attach to a 'B', although that may not have occurred to us when we cheerfully used that label. Perhaps even more importantly, they have psychological consequences. If we can secure acceptance that 'B' means 'A', then all the legitimacy invoked by an 'A', is assumed by a 'B'. The argument that I want to advance is that those who drafted the Charter did so on the assumption that the wellbeing and the integrity of a people, or of a nation, are equivalent to the integrity and wellbeing of the specific state to which they are attached on a one-to-one basis. I want to go on to argue that that proposition was never wholly true, and that it is becoming increasingly remote from the real world. I decided to begin by attempting definitions of the three words, but I quickly discovered that the task, if achievable, would require greater leisure, not to mention a wiser head, than is available to me. The first conclusion I reached is that all three words have eel-like qualities. When you think that you have grasped a meaning, it slips through your fingers. Not only do meanings change from generation to generation but they change contemporaneously according to the purpose of those who use them.

Depletion of CD34+ CD4+ cells in bone marrow from HIV-1-infected individuals.

Pancytopenia as a consequence of bone marrow abnormalities is commonly seen in HIV-infected individuals. To examine the effect that HIV-1 has on hematopoietic cells, we compared hematopoietic properties of bone marrow samples from HTV+ patients at various stages of disease with bone marrow samples from uninfected donors. While the absolute number of recovered CD34+ cells and the cloning efficiency of these cells did not differ significantly in HIV+ donors, the percentage of CD34+ CD4+ cells was significantly depleted in late-stage HIV+ patients. We observed a direct correlation between the numbers of CD34+ CD4+ cells in the bone marrow and the peripheral CD4 count. Further characterization of the CD34+ CD4+ subpopulation demonstrated that these cells expressed lower levels of HLA-DR on their surface compared with CD34+ CD4- cells, suggesting an immature phenotype. We also found evidence for expression of HIV-1 coreceptors CXCR-4 and CKR-5 message and protein in CD34+ bone marrow cells. While this finding suggested that hematopoietic cells might be susceptible to HIV infection at an early stage of maturation, thus affecting different cell lineages as they matured, we did not find any evidence for infection of HIV in these cells. These data suggest that HIV affects early hematopoietic progenitor cells either directly or indirectly, and in particular CD34+ CD4+ cells. This finding has important implications for disease pathogenesis and for application of gene therapy approaches that use CD34+ hematopoietic cells.

The treatment planning of segmental, conformal stereotactic radiosurgery utilizing a standard multileaf collimator.

Over a period of approximately 3 years, our institution has implemented and refined a system of Stereotactic Radiosurgery (SRS) which utilizes the standard multi leaf collimator (MLC) of the Scanditronix MM50 Racetrack Microtron and treats in an arrangement of segmental "pseudo-arcs." This system employs a commercial BRW based stereotactic frame which is mounted to the treatment table. With the exception of the table-mounted frame hardware there have been no modifications to the treatment machine to accommodate these treatments. By use of standard evaluation parameters (e.g., treatment time, planning time, dose conformance and dose heterogeneity ratios) this system compares quite favorably with reported data from institutions treating SRS with either a GammaKnife or a standard linear accelerator with tertiary collimators.

Oklahoma Firearm-Related Injury Surveillance.

CONTEXT: The magnitude of firearm-related deaths is known, but few studies have evaluated the magnitude and epidemiology of nonfatal firearm-related injuries. The circumstances resulting in fatal versus nonfatal injury are likely very different. No single data source provides complete details on nonfatal shootings. OBJECTIVE: To establish a surveillance system to define the epidemiology of fatal and nonfatal firearm-related injuries. DESIGN: Data were collected on fatal and nonfatal firearm-related injuries that occurred in 1995. SETTING: State of Oklahoma. PARTICIPANTS: Medical Examiner, Vital Statistics, hospital emergency and medical records departments, police departments, newspaper clipping service. MAIN OUTCOME MEASURES: Incidence rate of firearm-related injuries; case-fatality rate; demographic, medical, and epidemiologic data; sensitivity of each reporting source; completeness of reporting. RESULTS: The incidence rate of firearm-related injuries was 45.5 per 100,000 population. The case fatality rate was 35%. Injury rates were highest among adolescents, young adults, males, and African Americans. The Medical Examiner and Vital Statistics reported 87% and 98% of fatal cases, respectively. Passive surveillance of hospital emergency departments identified 72% of patients seeking hospital treatment. Among inpatients, 81% were identified by medical records departments. Newspaper clippings were obtained for 31% of cases. Information on the victim-perpetrator relationship and the type of firearm was available for 79% and 80% of cases, respectively. CONCLUSIONS: Statewide surveillance of firearm-related injuries using multiple data sources is possible and provides a picture of the overall firearm-related injury problem. Strategies to enhance computer linkages of medical and police data should be pursued to maximize the sensitivity of reporting and minimize the costs of surveillance.

Chromosomal duplication accompanies allelic loss in non-small cell lung carcinoma.

Hemizygous deletion in the short (p) arm of chromosome 3 is a common finding in non-small cell lung carcinoma (NSCLC) and is postulated to be a crucial early change in lung tumorigenesis. Yet one of the most frequent nuclear abnormalities in both NSCLC and premalignant bronchial epithelium is increase in chromosomal copy number. Deletion and duplication have not been assessed in the same tumor set by both molecular and cytogenetic methods to determine whether allelic loss correlates with chromosomal duplication in the same tumor cell populations. It is also not established what biological mechanisms might lead to allelic deletion and chromosomal duplication. We have investigated changes in the copy number of chromosome 3 in touch preparations of 38 NSCLCs (19 adenocarcinomas and 19 squamous cell carcinomas) using dual-target, dual-color fluorescence in situ hybridization (FISH) assays. Chromosome 3 centromere probe was matched with a 3p14.2 probe [intron 4 of the fragile histidine triad (FHIT) gene] and a 3p21.31 probe (HSemaIV gene). We then correlated FISH results with results of molecular analyses for allelic losses at loci in the regions to which the FISH probes mapped in 20 of these cases. Although various combinations of FISH abnormalities were sometimes detected within the same specimens, individual cases could be classified according to the predominant FISH pattern, usually with one abnormality present in >60% of tumor cells. Chromosomal duplication, indicated by the presence of more than two centromeric signals, was the most frequent abnormality observed by FISH and was accompanied by loss of specific sequences on 3p in approximately one-half of the specimens in which it was observed. The most frequent abnormality observed by molecular analysis was loss of heterozygosity (LOH) in both of the chromosomal regions tested and was demonstrated in 83% of cases with chromosomal duplication. We conclude that LOH may occur in the presence of chromosomal duplication, suggesting that the duplicated chromosome is homozygous. Our findings imply that LOH occurs before chromosomal duplication during lung carcinogenesis.

Diagnosis of fatty infiltration of the liver on contrast enhanced CT: limitations of liver-minus-spleen attenuation difference measurements.

BACKGROUND: We investigated whether liver-minus-spleen (L-S) attenuation differences can accurately diagnose fatty infiltration of the liver on contrast-enhanced computed tomography (CT). METHODS: A group of 78 patients administered a fast injection (90-s duration) of 150 mL 60% ionic contrast was compared with 81 patients given a slow injection (152.5 s). The presence or absence of fatty infiltration of the liver was diagnosed by noncontrast CT. RESULTS: The L-S attenuation differences varied significantly, depending on both injection rate and timing of measurements. For the fast-injection group, the optimal L-S threshold for diagnosing fatty infiltration ranged from -43 to -33 Hounsfield units (HU) for early (79 s) and late measurements (106 s), respectively. For the slow-injection group, the optimal threshold ranged from -31 to -25 HU (80 and 112 s, respectively). In addition, sensitivity was not very high (range = 0.54-0.71) for either injection protocol at any measurement time because of significant overlap of L-S values between normal and fatty infiltration patients. Moderate and severe fatty infiltration were more reliably diagnosed than mild fatty infiltration by this method. CONCLUSIONS: Contrast injection rate and timing of measurements significantly influence the optimal L-S threshold for diagnosing fatty liver. This limits the clinical usefulness of such measurements.