Eight-Year Estimates of Methane Emissions from Oil and Gas Operations in Western Canada Are Nearly Twice Those Reported in Inventories.

The provinces of Alberta and Saskatchewan account for 70% of Canada's methane emissions from the oil and gas sector. In 2018, the Government of Canada introduced methane regulations to reduce emissions from the sector by 40-45% from the 2012 levels by 2025. Complementary to inventory accounting methods, the effectiveness of regulatory practices to reduce emissions can be assessed using atmospheric measurements and inverse models. Total anthropogenic (oil and gas, agriculture, and waste) emission rates of methane from 2010 to 2017 in Alberta and Saskatchewan were derived using hourly atmospheric methane measurements over a six-month winter period from October to March. Scaling up the winter estimate to annual indicated an anthropogenic emission rate of 3.7 ± 0.7 MtCH4/year, about 60% greater than that reported in Canada's National Inventory Report (2.3 MtCH4). This discrepancy is tied primarily to the oil and gas sector emissions as the reported emissions from livestock operations (0.6 MtCH4) are well substantiated in both top-down and bottom-up estimates and waste management (0.1 MtCH4) emissions are small. The resulting estimate of 3.0 MtCH4 from the oil and gas sector is nearly twice that reported in Canada's National Inventory (1.6 MtCH4).

An atmospheric perspective on North American carbon dioxide exchange: CarbonTracker.

We present an estimate of net CO(2) exchange between the terrestrial biosphere and the atmosphere across North America for every week in the period 2000 through 2005. This estimate is derived from a set of 28,000 CO(2) mole fraction observations in the global atmosphere that are fed into a state-of-the-art data assimilation system for CO(2) called CarbonTracker. By design, the surface fluxes produced in CarbonTracker are consistent with the recent history of CO(2) in the atmosphere and provide constraints on the net carbon flux independent from national inventories derived from accounting efforts. We find the North American terrestrial biosphere to have absorbed -0.65 PgC/yr (1 petagram = 10(15) g; negative signs are used for carbon sinks) averaged over the period studied, partly offsetting the estimated 1.85 PgC/yr release by fossil fuel burning and cement manufacturing. Uncertainty on this estimate is derived from a set of sensitivity experiments and places the sink within a range of -0.4 to -1.0 PgC/yr. The estimated sink is located mainly in the deciduous forests along the East Coast (32%) and the boreal coniferous forests (22%). Terrestrial uptake fell to -0.32 PgC/yr during the large-scale drought of 2002, suggesting sensitivity of the contemporary carbon sinks to climate extremes. CarbonTracker results are in excellent agreement with a wide collection of carbon inventories that form the basis of the first North American State of the Carbon Cycle Report (SOCCR), to be released in 2007. All CarbonTracker results are freely available at http://carbontracker.noaa.gov.

The complex nature of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes.

OBJECTIVE: To describe the systematic analysis of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes, characterise the structural chromosome rearrangements, map the translocation breakpoints, and report detectable genomic imbalances. METHODS: DNA microarrays were used with a resolution of 1 Mb for the detailed genome-wide analysis of the patients. Array CGH was used to screen for genomic imbalance and array painting to map chromosome breakpoints rapidly. These two methods facilitate rapid analysis of translocation breakpoints and screening for cryptic chromosome imbalance. Breakpoints of rearrangements were further refined (to the level of spanning clones) using fluorescence in situ hybridisation where appropriate. RESULTS: Unexpected additional complexity or genome imbalance was found in six of 10 patients studied. The patients could be grouped according to the general nature of the karyotype rearrangement as follows: (A) three cases with complex multiple rearrangements including deletions, inversions, and insertions at or near one or both breakpoints; (B) three cases in which, while the translocations appeared to be balanced, microarray analysis identified previously unrecognised imbalance on chromosomes unrelated to the translocation; (C) four cases in which the translocation breakpoints appeared simple and balanced at the resolution used. CONCLUSIONS: This high level of unexpected rearrangement complexity, if generally confirmed in the study of further patients, will have an impact on current diagnostic investigations of this type and provides an argument for the more widespread adoption of microarray analysis or other high resolution genome-wide screens for chromosome imbalance and rearrangement.

Administrative relationships between community mental health centers and academic psychiatry departments: a 12-year update.

OBJECTIVE: The authors investigated the administrative relationships in 1990 between medical school departments of psychiatry and community mental health centers (CMHCs). METHOD: A 20-item questionnaire was sent to the chairpersons of the 110 medical school departments of psychiatry with accredited psychiatric residencies. RESULTS: Sixty-nine percent of the chairpersons responded to the questionnaire. Sixty-eight percent of the responding chairpersons reported that their departments had relationships with CMHCs, and 90% of these relationships involved the education of psychiatric residents. Most responding chairpersons described the quality of their existing CMHC relationships as good to excellent. In the most common type of relationship reported the CMHC was used as a setting for resident education. The vast majority of responding chairpersons stated that quality resident education is possible in a CMHC, and about two-thirds of the responding chairpersons with CMHC relationships involving residency education rated the CMHC rotation as of major importance to their residency programs. CONCLUSIONS: CMHCs continue to be an important and valued component of the educational experience for many psychiatric residents, and many departments of psychiatry have recognized the advantages and benefits of CMHCs for residency training. There are now considerable data on how a relationship between a medical school department and a CMHC should be structured to achieve maximum benefit for both the department and the CMHC.

[Data processing and QA/QC of atmosphere CO2 and CH4 concentrations by a method of GC-FID in-situ measurement at Waliguan station].

To strengthen scientific management and sharing of greenhouse gas data obtained from atmospheric background stations in China, it is important to ensure the standardization of observations and establish the data treatment and quality control procedure so as to maintain consistency in atmospheric carbon dioxide (CO2) and methane (CH4) measurements from different background stations. An automated gas chromatographic system (Hewlett Packard 5890GC employing flame ionization detection) for in situ measurements of atmospheric CO2 and CH4 has been developed since 1994 at the China Global Atmosphere Watch Baseline Observatory at Mt. Waliguan, in Qinhai. In this study, processing and quality control flow of CO2 and CH4 data acquired by HP ChemStation are discussed in detail, including raw data acquisition, data merge, time series inspection, operator flag, principal investigator flag, and the comparison of the GC measurement with the flask method. Atmosphere CO2 and CH4 mixing ratios were separated as background and non-background data using a robust local regression method, approximately 72% and 44% observed values had been filtered as background data for CO2 and CH4, respectively. Comparison of the CO1 and CH, in situ data to the flask sampling data were in good agreement, the relative deviations are within +/- 0.5% for CO2 and for CH4. The data has been assimilated into global database (Globalview-CO2, Globalview-CH4), submitted to the World Data Centre for Greenhouse Gases (WDCGG), and applied to World Meteorological Organization (WMO) Greenhouse Gas Bulletin and assessment reports of the United Nations Intergovernmental Panel on Climate Change (IPCC).

Blood disoprofol levels in anesthetised patients. Correlation of concentrations after single or repeated doses with hypnotic activity.

The blood concentrations of disoprofol (Diprivan) after single intravenous doses of 1, 2 or 3 mg/kg have been examined in a subpopulation from previously reported clinical studies. The linear relationship between sleep time and dose could be explained by the linearity of the pharmacokinetics at these doses. After a single injection the awakening concentration was independent of dose, with a mean value of 1.04 micrograms/ml. No acute tolerance occurred with disoprofol. On repeated 1 mg/kg bolus injections the sleeping time rose initially but stabilised after four doses. The waking concentration was independent of the number of doses administered. The clinical findings fitted an agent with a very rapid distribution phase and a short elimination half-life.

Pharmacokinetics of propofol (diprivan) in elderly patients.

The pharmacokinetics of propofol (2,6 diisopropylphenol) were compared in 12 patients aged 65-80 yr and 12 patients aged 18-35 yr. After premedication with papaveretum i.m., anaesthesia was induced with propofol 2.0 mg kg-1 in the elderly and 2.5 mg kg-1 in the younger patients. Alcuronium 12-20 mg was then given and the patient's lungs ventilated with halothane and nitrous oxide in oxygen. Blood was taken after various time intervals up to 24 h for the measurement of propofol concentrations by HPLC and for the estimation of propofol protein binding. The mean blood propofol concentration was generally higher in the elderly group, but this difference was only significant at 2 min after induction. The clearance of propofol was significantly lower in the elderly (1.44 +/- 0.10 (SE) litre min-1) than in the younger patients (1.79 +/- 0.12 litre min-1). The volume of the central compartment in the elderly patients was significantly smaller (19.6 +/- 5.2 litre) than that in the young (26.3 +/- 2.9 litre). There was no difference in the volume of distribution at equilibrium (1608 +/- 246 litre in the elderly and 1757 +/- 360 litre in the young), in the volume of distribution at steady state (691 +/- 139 litre in the elderly and 771 +/- 236 litre in the young) or in the half-lives of distribution and elimination. The plasma protein binding of propofol was similar in both groups and showed no trend with time after dose.

Disposition of propofol in patients undergoing surgery. A comparison in men and women.

The disposition kinetics of propofol have been determined in 12 patients (six female) receiving propofol 2.5 mg kg-1 for induction of anaesthesia, which was maintained with 67% nitrous oxide in oxygen and 1-1.5% halothane. Peripheral blood samples were collected at selected times up to 8 h after the injection of the drug, and whole blood propofol concentrations determined by HPLC with fluorescence detection. Drug concentration-time data were analysed by the non-linear regression program ELSFIT. This showed the data to be describable by a tri-exponential equation, corresponding to a three-compartment model. There were no differences in the derived kinetic indices for the male and female patients, with the exception of a greater Vdss:V gamma ratio in the males. The terminal half-life in the male patients was 262 min (SEM 44), and in the female patients 309 min (60). Vdss was 329 litre (67) and 313 litre (69) in male and female patients, respectively. The clearance in both groups was 1.8 litre min-1. Seven out of 12 patients showed significant secondary peaks in blood propofol concentration associated with recovery from anaesthesia.

The pharmacokinetics of propofol in laboratory animals.

1. The pharmacokinetics of propofol in an emulsion formulation ('Diprivan') have been studied after single bolus doses to rats, dogs, rabbits and pigs, and after single and multiple infusions to dogs. Venous blood propofol concentrations were determined by h.p.l.c. with u.v. or fluorescence detection. Curve fitting was performed using ELSFIT. 2. The distribution of propofol in blood and its plasma protein binding have been studied in rat, dog, rabbit and man. Protein binding was high (96-98%), and in most species propofol showed appreciable association with the formed elements of blood. 3. Where an adequate sampling period was employed the pharmacokinetics of propofol were best described by a three-compartment open 'mammillary' model. Propofol was distributed into a large initial volume (1-21/kg) and extensively redistributed (Vss = 2-10 x body weight) in all species. Clearance of propofol by all species was rapid, ranging from about 30-80 ml/kg per min in rats, dogs and pigs to about 340 ml/kg per min in rabbits.

Pharmacokinetics of propofol during and after long-term continuous infusion for maintenance of sedation in ICU patients.

The pharmacokinetics of propofol administered as long term infusions were determined in 12 intensive care unit patients (two female; mean age 58 yr, mean weight 66.9 kg) requiring sedation during mechanical ventilation. Patients were recruited after having been administered propofol for 24 h. Blood samples for analysis of propofol were taken during the infusion (mean duration 85.6 h; mean rate 2.58 mg kg-1 h-1) and for up to about 42 h after its termination. The median propofol total body clearance, derived from the apparent steady state propofol blood concentrations during infusion, was 2.11 litre min-1. One patient died during the infusion, from multi-organ failure secondary to a pre-existing septicaemia, and in one other patient no sampling was possible during the first 30 min after infusion; full elimination data were obtained for 10 patients. After termination of the infusion, propofol blood concentrations declined rapidly, with an overall mean decrease of 50% over the first 10 min; thereafter the decline was more gradual. The elimination profile was triphasic in seven patients and biphasic in three patients. Mean half-lives for the three phases were 1.81 (n = 10) min, 70.9 (n = 7) min and 1411 (n = 11) min. There was no apparent trend in the terminal phase half-life with the duration of sampling after infusion.

Disposition of propofol administered as constant rate intravenous infusions in humans.

The disposition of the intravenous anesthetic propofol was studied when administered as a constant rate infusion at 3, 6, and 9 mg.kg-1.hr-1 for at least 2 hr to three groups of six patients each undergoing surgery under regional anesthesia. Arterial blood samples were collected at selected times during and up to 8 hr after infusion. Whole blood propofol concentrations were determined by high-performance liquid chromatography with fluorescence detection. Using a non-linear least-squares regression analysis, the individual data sets were best fitted by a three-compartment open mamillary model with central elimination in 17 patients. In one patient a biexponential equation was more appropriate. Derived pharmacokinetic parameters expressed as mean values +/- SD indicated an initial fast distribution (t1/2 pi; 2.8 +/- 1.2 min), with an intermediate phase (t1/2 alpha; 31.4 +/- 14.7 min), and a long terminal phase (t1/2 beta; 355 +/- 227 min), a large volume of distribution at steady state (Vss, 287 +/- 213 L), and a high blood clearance (Clb, 1.7 +/- 0.3 L/min). The function of drug in the central compartment in the terminal phase was low (Fc, 0.02). The elimination rate constant (K10, 0.1190 +/- 0.0351 min-1) was large compared with the other transfer rate constants and was responsible for the large amount of drug eliminated during distribution. The fraction of drug eliminated during the terminal phase amounted to 0.28. The slow return of drug from remote tissues (K31, 0.0033 +/- 0.0013 min-1) was rate limiting in the ultimate elimination.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of propofol in female patients. Studies using single bolus injections.

The pharmacokinetics of propofol in a dose of 2.5 mg kg-1 given via a vein in the antecubital fossa were studied in 18 patients. Anaesthesia was maintained with nitrous oxide in oxygen in all patients. The effects of pretreatment with fentanyl (n = 6) and maintenance with halothane (n = 6) on the pharmacokinetics of propofol were also investigated. Pretreatment with fentanyl resulted in prolonged apnoea in four patients. No serious side effects occurred. The pharmacokinetics of propofol in unpretreated patients who were maintained with nitrous oxide in oxygen only can be described by a three-compartment open mammalian model with very rapid distribution (T1/2 alpha about 3 min), rapid elimination (T1/2 beta 45 min) and a slower final phase (T1/2 gamma about 300 min). The total body clearance of propofol was rapid (1.91 litre min-1). Propofol was initially distributed into a relatively large central compartment (41.3 litre) and was extensively redistributed (Vss 305 litre; V gamma 722 litre). Throughout the sampling period the mean blood concentrations of propofol for the patients pretreated with fentanyl were about 50% higher than the mean concentrations for patients maintained with nitrous oxide only. Mean propofol concentrations for the patients maintained with halothane were intermediate between those of the other two groups.

Pharmacokinetic evaluation of ICI 35 868 in man. Single induction doses with different rates of injection.

Blood concentrations of ICI 35 868 have been measured in patients following a single bolus dose of 2 mg kg-1. Three different rates of injection of the anaesthetic agent (3-5s, 20s and 40 or 50s) were examined. Pharmacokinetic indices, derived from blood concentrations of ICI 35 868, were independent of the speed of injection. The blood profiles could be described by a two-compartment open model with a mean alpha-phase half-life of 2.5 min and a mean beta-phase half-life of 54.5 min. The mean total body clearance was 3454 ml min-1. Similar data were obtained from a 4-mg kg-1 dose. The mean recovery time (4.4 min) and concentration of ICI 35 868 at awakening (1.05 micrograms ml-1) were also independent of the rate of injection. Using the derived pharmacokinetic model, predictions of drug concentrations have been made for repeated bolus doses, or infusions, of ICI 35 868.

Pharmacokinetics of propofol ('Diprivan') as an induction agent.

The disposition kinetics of propofol have been determined in 12 patients (6 female) receiving 2.5 mg/kg for induction of anaesthesia which was maintained using 1.5% halothane and 67% nitrous oxide in oxygen. Patients were premedicated with oral diazepam 10 mg and were undergoing body surface surgery. Peripheral venous samples were collected up to 8 h after injection of the drug. Whole blood propofol concentrations were determined by high pressure liquid chromatography using fluorescence detection. Data analysis indicates a 3 compartment model, with a terminal half-life of 286 (s.e.m. +/- 36) min, clearance of 1803 +/- 125 ml/min, and volume of distribution of 755 +/- 109 litres. These values are significantly different from those reported previously by Adam et al., (1983) for the Cremophor formulation of the drug. Seven of the patients showed significant secondary peaks of the blood concentration associated with recovery from anaesthesia.

A ten-year update of administrative relationships between state hospitals and academic psychiatry departments.

OBJECTIVE: In a follow-up to a survey ten years earlier, the authors investigated current administrative relationships between academic departments of psychiatry and state hospitals. METHODS: A 20-item questionnaire was sent to the chairs of the 110 medical school departments of psychiatry with accredited psychiatric residencies. RESULTS: Eighty-two departments, or 75 percent, responded. Seventy-one percent of the respondents reported that their department had a relationship with a state hospital; 79 percent of these relationships involved the education of psychiatric residents. Most respondents rated the quality of the relationship favorably (4 or 5 on a 5-point scale). Almost all respondents believed that residents can obtain a high-quality education in a state hospital. More than half of the departments responding to a question about the importance of a state hospital rotation rated it of major importance in their residency program. CONCLUSIONS: Many medical school departments of psychiatry remain closely involved with state hospitals and recognize the hospital as an important part of residents' education. Administrators have gained much experience about how to develop and implement mutually beneficial relationships.

Species differences in blood profiles, metabolism and excretion of 14C-propofol after intravenous dosing to rat, dog and rabbit.

1. Bolus i.v. doses of 14C-propofol (7-10 mg/kg) to rat, dog and rabbit, or an infusion dose (0.47 mg/kg per min for 6 h) to dog were eliminated primarily in urine (60-95% dose); faecal elimination (13-31%) occurred for rat and dog, but was minimal (less than 2%) for rabbit. 2. After bolus administration, blood 14C concentrations were maximal (8-30 micrograms equiv./ml) at 2-15 min; these declined rapidly during the 0-2 h period and thereafter more slowly. Propofol concentrations were maximal (4-16 micrograms/ml) at 2 min and the profiles were best fitted by a tri-exponential (rat and dog) or bi-exponential (rabbit) equation. Duration of sleep ranged from 5 to 8 min. 3. Infusion of 14C-propofol in dog gave a blood 14C concentration of 117 micrograms equiv./ml at the end of the 6 h infusion period; this declined at a similar rate to that after the bolus dose. Propofol concentration on termination of infusion was 13 micrograms/ml; thereafter, propofol concentrations declined less rapidly than after the bolus dose. Waking occurred about 44 min post-infusion. 4. Propofol was cleared by conjugation of the parent molecule or its quinol metabolite; hydroxylation of an isopropyl group also occurred in rat and rabbit. Biliary excretion leading to enterohepatic recirculation, and in turn increased sulphate conjugation, occurred in rat and dog, but not rabbit, resulting in a marked interspecies variation in drug clearance and metabolite profiles.

Distribution in female rats of an anaesthetic intravenous dose of 14C-propofol.

1. Bolus i.v. doses of 14C-propofol (9 mg/kg) were administered to female rats for measurement of tissue levels of total 14C and propofol from 2 min to 24 h post-dose; whole-body autoradiography was studied at 6 min, 2 h and 24 h post-dose, and also involved 15-day pregnant rats. 2. The blood propofol concentration-time profile was fitted by a tri-exponential function corresponding to a three-compartment open model. Data show rapid distribution during the mixing period into highly perfused tissues and muscle, comprising the central compartment, and slower uptake into less well-perfused skin and adipose tissues comprising the deeper compartments. 3. The initial decline in blood propofol concentration was associated with redistribution (t1/2 4 min), the second decline (15-240 min post-dose) was associated with metabolism (t1/2 33 min) and the third decline reflected slow depletion of drug from deep tissue compartments (t1/2 6.4 h). 4. Blood and brain propofol concentrations on waking (at 7 min post-dose) were 4 micrograms/ml and 9 micrograms/g respectively; the model shows that, at this time, 30% of the dose was lost from the central compartment by redistribution and a similar amount by metabolism. 5. Tissue profiles of total 14C and propofol diverged for highly perfused tissues (other than brain) because of slow clearance of metabolites, accentuated by enterohepatic recirculation.

Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of 14C-propofol.

1. An intravenous dose of 14C-propofol (0.47 mg/kg) administered to six male volunteers was rapidly eliminated with 88% recovered in the urine in 5 days and less than 2% in faeces. 2. The dose was cleared by metabolism with less than 0.3% excreted unchanged. The major metabolites were the glucuronic acid conjugate of propofol and the glucuronic acid and sulphate conjugates of its hydroxylated derivative, 2,6-diisopropyl-1,4-quinol. Propofol glucuronide accounted for about 53% of the urinary radioactivity and was the major metabolite in plasma from 30 min post dose. 3. The blood concentration of propofol declined in a biphasic manner from a maximum mean value of 0.44 microgram/ml, 2 min after injection. The half-lives of the first and second exponential phases, mean values 5 min and 97 min respectively, varied widely among subjects. A proportion of the dose was cleared slowly, probably due to slow release from less well perfused tissues. Propofol accounted for 94% of the total blood radioactivity at 2 min but only about 6% from 3 to 8 h post dose. 4. Propofol has a volume of distribution equivalent to about 3 to 4 times body weight, and a mean total body clearance of 2.2 1/min.

Propofol metabolism in man during the anhepatic and reperfusion phases of liver transplantation.

1. An i.v. dose of 14C-propofol (0.53 mg/kg) was administered to three male and three female patients during the anhepatic phase of liver transplantation, which lasted 30-56 min after dosing. Arterial and venous blood samples, bile (T-tube drainage) and urine were collected at various times afterwards and submitted to h.p.l.c. and radioassay or specific fluorescence detection for the unchanged drug. 2. Extrahepatic metabolism was apparent during the anhepatic phase, since at 30 min post-dose, unchanged propofol comprised only 42-89% of the blood radioactivity. 3. Examination of the plasma radioactivity during the anhepatic phase in two subjects showed evidence of propofol glucuronide and 4-quinol sulphate, confirming extrahepatic metabolism of the drug. Quinol glucuronides were only detected in the liver reperfusion phase. 4. There was no evidence that the lungs contribute to the extrahepatic metabolism of propofol, since drug concentrations in the arterial blood were not less than in central venous samples. 5. During the first 24 h period, urine collected from five patients contained 7-74% dose, whilst the bile contained 0.1-0.9%. In three patients with normal renal function recovery in urine was 66-74% dose. Examination of urinary radioactivity in one subject showed the main component to be propofol glucuronide during the anhepatic phase.