The goal of this study is to evaluate a version of the ensemble-variational data assimilation approach (EnVar) for possible replacement of 4D-Var at Environment Canada for global deterministic weather prediction. This implementation of EnVar relies on 4-D ensemble covariances, obtained from an ensemble Kalman filter, that are combined in a vertically dependent weighted average with simple static covariances. Verification results are presented from a set of data assimilation experiments over two separate 6-week periods that used assimilated observations and model configuration very similar to the currently operational system. To help interpret the comparison of EnVar versus 4D-Var, additional experiments using 3D-Var and a version of EnVar with only 3-D ensemble covariances are also evaluated. To improve the rate of convergence for all approaches evaluated (including EnVar), an estimate of the cost function Hessian generated by the quasi-Newton minimization algorithm is cycled from one analysis to the next. Analyses from EnVar (with 4-D ensemble covariances) nearly always produce improved, and never degraded, forecasts when compared with 3D-Var. Comparisons with 4D-Var show that forecasts from EnVar analyses have either similar or better scores in the troposphere of the tropics and the winter extra-tropical region. However, in the summer extra-tropical region the medium-range forecasts from EnVar have either similar or worse scores than 4D-Var in the troposphere. In contrast, the 6 h forecasts from EnVar are significantly better than 4D-Var relative to radiosonde observations for both periods and in all regions. The use of 4-D versus 3-D ensemble covariances only results in small improvements in forecast quality. By contrast, the improvements from using 4D-Var versus 3D-Var are much larger. Measurement of the fit of the background and analyzed states to the observations suggests that EnVar and 4D-Var can both make better use of observations distributed over time than 3D-Var. In summary, the results from this study suggest that the EnVar approach is a viable alternative to 4D-Var, especially when the simplicity and computational efficiency of EnVar are considered. Additional research is required to understand the seasonal dependence of the difference in forecast quality between EnVar and 4D-Var in the extra-tropics.

In May 2008, several important changes with respect to satellite data assimilation were made to the Meteorological Service of Canada (MSC) operational global 4D-Var Data Assimilation and Forecast System (DAFS). At the same time, a new version of the MSC DAFS has been developed which uses a new version of the MSC Global Environmental Multiscale (GEM) model called GEM-Strato. The GEMStrato model incorporates several significant changes to the current version of the model, including a lid raised from 10 hPa (~30 km) to 0.1 hPa (~65 km). The new system, scheduled to replace the current system in 2009, allows for assimilation of additional radiance data from higher-peaking microwave and infrared instrument channels as well as GPS radio-occultation data up to 40 km (~3 hPa). This paper describes the recent changes in satellite data assimilation in the operational DAFS, and presents results of satellite data impact experiments with the new GEM-Strato system. In addition, the performance of the operational DAFS and the new GEM-Strato system are compared. Finally, future plans for satellite data assimilation are presented, which include assimilation of data from the EUMETSAT satellites METOP (AMSU-A, MHS, IASI, GRAS, ASCAT) and METEOSAT.

In 2003, strong energetic particle precipitation (EPP) events occurred producing massive amounts of ionization which affected the polar region significantly perturbing its chemical state down to the middle stratosphere. These events and their effects are generally left unaccounted for in current models of stratospheric chemistry and large differences between observations and models are then noted. In this study, we use a coupled 3-D stratospheric dynamical-chemical model and assimilation system to ingest MIPAS temperature and chemical observations. The goal is to gain further understanding of assimilation and monitoring processes during EPP events and their impacts on the stratospheric polar chemistry. Moreover, we investigate the feasibility of assimilating valid "outlier" observations associated with such events. We use OmF (Observation minus Forecast) residuals as they filter out phenomena well reproduced by the model (such as gas phase chemistry, transport, diurnal and seasonal cycles) thus revealing a clear trace of the EPP. Inspection of OmF statistics in both passive (without chemical assimilation) and active (with chemical assimilation) cases altogether provides a powerful diagnostic tool to assess the model and assimilation system. We also show that passive OmF can permit a satisfactory evaluation of the ozone partial column loss due to EPP effects. Results suggest a small but significant loss of 5–6 DU (Dobson Units) during an EPP-IE (EPP Indirect Effects) event in the Antarctic winter of 2003, and about only 1 DU for the SPE (Solar Proton Event) of October/November 2003. Despite large differences between the model and MIPAS chemical observations (NO2, HNO3, CH4 and O3), we demonstrate that a careful assimilation with only gas phase chemistry included in the model (i.e. no provision for EPP) and with relaxed quality control nearly eliminated the short-term bias and significantly reduced the standard deviation error of the constituents below 1 hPa.

The objective of this study is to investigate the impact on temperature forecast of using ozone analyses for the computation of heating rates in a three-dimensional variational data assimilation (3D-Var) system with a coupled model. The system is based on a tropospheric-stratospheric forecast model that includes a comprehensive stratospheric chemistry module for online resolution of the dynamical, radiative, and photochemical interactions. The system assimilates conventional observations as well as temperature and ozone measurements from the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) instrument. Several data assimilation cycles have been performed over the period August-October 2003 to produce a set of analyses that have been used for launching an ensemble of 10-day forecasts. Temperature and ozone forecasts have been compared with MIPAS and radiosonde observations in different regions. Results show that, in the absence of ozone assimilation, the impact of using a prognostic ozone distribution for the computation of heating rates as opposed to monthly mean climatologies is generally neutral. With the addition of ozone assimilation, the improvement against a noninteractive assimilation system is systematic and occurs over a wide range of time scales throughout the lower stratosphere. The improvement on 6-h temperature forecasts is mainly seen in the Southern Hemisphere, where ozone analyses are in good agreement with observations. For 10-day forecasts, the impact of using ozone analyses is more important in the Northern Hemisphere, where it improves the temperature predictability by more than 1 day at 50 hPa. Comparisons with analyses also show a systematic reduction of the temperature root-mean-square errors and biases throughout the assimilation period. The overall results demonstrate that a comprehensive coupled 3D-Var system that incorporates the radiative feedback from ozone analyses can be used for improving temperature predictability throughout the stratosphere. Comprehensive approaches can be used as a benchmark for the development of linearized methods for improving temperature and ozone forecasting in the region.

Aboriginal peoples are over-represented in the Canadian corrections system. When released, they face challenges. Many return to the communities where their friends and family are but have few housing, educational, and employment opportunities, and have difficult choices to make. This participatory research study included interviews with 30 Aboriginal men who had done jail time and had lived in the downtown core of a major Canadian prairie city. It revealed five overlapping themes describing the experience of being released, getting by, finding a community that would receive them, staying out of jail, and trying to get ahead. The results indicate that there is a gap in services for Aboriginal men who have done jail time, and that housing models to meet this need should be developed with the input of residents in local communities.

Environment Canada is currently planning to raise the lid of its operational global forecast model GEM (Global Environmental Multiscale) from 10 hPa (~30 km) to 0.1 hPa (~60 km) in the first quarter of 2009. The new version is called GEM-Strato. This project has several major components: changes to the model physics, new vertical coordinate, new background error statistics, and additional data types for the assimilation system. These include AMSU-A stratospheric channels 11-14 in addition to data types recently implemented operationally: AIRS and SSM/I radiances and Quickscat oceanic winds. This paper presents results on the impact of the new model configuration, followed by that of adding the new data types mentioned above, and that from GPS-RO refractivity profiles in the variational assimilation system.

Biopharmaceutics & Drug DispositionVolume 5, Issue 1 p. 97-100 Research Paper Pharmacokinetic evaluation of a conventional and controlled release product of betamethasone J. C. K. Loo, J. C. K. Loo Bureau of Drug Research, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario, Canada K1A 0L2Search for more papers by this authorN. Jordan, N. Jordan Bureau of Drug Research, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario, Canada K1A 0L2Search for more papers by this authorC. Charette, C. Charette Bureau of Drug Research, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario, Canada K1A 0L2Search for more papers by this authorR. Brien, R. Brien Bureau of Drug Research, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario, Canada K1A 0L2Search for more papers by this authorI. J. McGilveray, I. J. McGilveray Bureau of Drug Research, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario, Canada K1A 0L2Search for more papers by this author J. C. K. Loo, J. C. K. Loo Bureau of Drug Research, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario, Canada K1A 0L2Search for more papers by this authorN. Jordan, N. Jordan Bureau of Drug Research, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario, Canada K1A 0L2Search for more papers by this authorC. Charette, C. Charette Bureau of Drug Research, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario, Canada K1A 0L2Search for more papers by this authorR. Brien, R. Brien Bureau of Drug Research, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario, Canada K1A 0L2Search for more papers by this authorI. J. McGilveray, I. J. McGilveray Bureau of Drug Research, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario, Canada K1A 0L2Search for more papers by this author First published: January/March 1984 https://doi.org/10.1002/bdd.2510050113Citations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 J. C. K. Loo, I. J. McGilveray, N. Jordan and R. Brien, Biopharm. Drug Dispos., 2, 265 (1981). 2 K. Yamaoka, T. Nakagawa and T. Uno, J. Pharmacokinet. Biopharm., 6, 547 (1978). 3 S. Riegelman and P. Collier, J. Pharmacokinet. Biopharm., 8, 509 (1980). 4 J. C. K. Loo, C. Charette, N. Jordan and I. J. McGilveray, in Pharmacokinetics: A Modern View, L. Z. Benet and G. Levy (Eds), Plenum, New York (in press). Citing Literature Volume5, Issue1January/March 1984Pages 97-100 ReferencesRelatedInformation

A high-performance liquid chromatographic procedure is described for the determination of disopyramide and its mono-N-dealkyl metabolite which offers simplicity of extraction with excellent selectivity, sensitivity and reproducibility. The drug and metabolite, following basic diethyl ether extraction and back-extraction with acetic acid, are injected into a reversed-phase high-performance liquid chromatographic column and the absorbance of the eluate measured at 254 nm. Detectability limits of 0.05 micrograms/ml were obtained with both compounds, and studies of the reproducibility, precision, recovery, stability during storage and effect of time in separating plasma from erythrocytes are described. Applications of this high-performance liquid chromatographic procedure to plasma samples from patients on disopyramide therapy and to plasma and urine from a healthy dog administered single doses are reported.

This chapter discusses maprotiline hydrochloride. Maprotiline hydrochloride occurs as a white to off-white, odorless, fine, crystalline powder. Maprotiline hydrochloride is polymorphic and known to exhibit several crystal forms. A typical production batch is a mixture with varying ratios of crystal form A and B. The two crystal forms show no difference in solubility characteristics at room and physiological temperatures. The existence of polymorphism has also been shown by differential scanning calorimetry. A typical batch of maprotiline hydrochloride frequently exhibits two melt endotherms indicating the presence of two crystal forms. Maprotiline hydrochloride is freely soluble in methanol and chloroform, slightly soluble in water, and practically insoluble in isooctane. Maprotiline hydrochloride is best identified by: infrared absorption, ultraviolet absorption, and a test for chloride.

The bioavailabilities of eight quinidine sulfate, two gluconate, and one polygalacturonate formulations were compared, with one of the sulfate formulations as a reference (R) in a panel of 24 volunteers, according to a design comprising duplicate 6 x 6 Latin squares in two subject groups. Only one gluconate formulation (H) gave a significantly lower (p less than 0.05) area under the curve from 0 to 30 hr (AUC30), 90% or R, which was not as significant as AUC infinity (94% of R). Formulation H also gave a significantly lower peak concentration (Cmax) and a longer time to peak concentration (tmax) and generally exhibited some characteristics of sustained-release product. In addition, one product (F) gave a significantly higher Cmax while another formulation (D) gave a longer tmax. The wide range of dissolution times obtained with these products with three test conditions was not reflected in the AUC, Cmax, or tmax values obtained, except the Formulation H was consistently the slowest to dissolve. The terminal rate constants, expressed as t 1/2, of the 24 subjects gave an overall mean of 7.49 +/- 0.77 hr and ranged from 6.24 +/- 0.28 to 0.49 +/- 0.90 hr in individuals. The estimated total body clearance, with the assumption that the oral bioavailability was 70%, gave an overall mean of 4.22 +/- 1.05 and ranged from 2.49 +/- 0.28 to 6.42 +/- 0.70 mg/min/kg in individuals, demonstrating the wide range of quinidine disposition even in healthy subjects; this finding is in agreement with recently published results.

A gas-liquid chromatographic procedure employing an alkali flame ionization detector (GLC-AFID) for the quantitation of imipramine and its major active metabolite, desipramine, in plasma was developed. This method validated a previously reported radioimmunoassay for imipramine and desipramine. The GLC-AFID method was also compared with a GLC-mass spectrometric procedure which employed selected ion monitoring (GLC/MS-SIM) in which specific ions for imipramine and desipramine were monitored. The two methods using gas chromatographic separation were shown to be suitable for therapeutic monitoring of these drugs in patients. The direct immunoassay, which measures the total imipramine plus desipramine, is very useful when large numbers of samples are to be analysed rapidly and it compares favorably with the other two analytical procedures.

The mass spectra of the tristrifluoroacetyl derivative of α-methyldopamine and the bistrifluoroacetyl derivative of 3-O-methyl-α-methyldopamine contain important ions which can be rationalized by two alternative fragmentation pathways. These ambiguities were resolved by means of a simple chemical derivatization technique. The labile phenolic ester groups were hydrolyzed and subsequently re-esterified by reaction with chlorodifluoroacetic anhydride in the presence of ethyl acetate thereby labeling ions containing ester group(s) in the mass spectra with the diagnostic chlorine isotope ratio. This resulted in the addition of 16/18 mass units to the weights of the ions for each fluorine atom replaced by chlorine. Since it was easy to distinguish loss of the mass of a neutral molecule of trifluoroacetamide (113 mass units) from the ions of a chlorodifluoroacetoxy radical (129 mass units), the elimination of trifluoroacetamide was distinguished from that of trifluoroacetoxy radical. Derivatives were also prepared in which the chlorine label was located on the N-acyl function. The mass spectra of the chlorine labeled compounds showed that the major fragmentation pathway of tristrihaloacetyl-α-methyldopamine and bistrihaloacyl-3-O-methyl-α-methyldopamine is by loss of a neutral molecule of trihaloacetamide.

For the development of radioimmunoassay procedures for tricyclic antidepressants, two drug haptens were synthesized for each of the two amitriptyline-nortriptyline and imipramine-desipramine groups. In one case, nortriptyline or desipramine was treated with succinic anhydride to yield N-(3-carboxypropionyl) derivatives; in the other case, the haptens were novel, N-(2-carboxyethyl) derivatives. The hapten and its corresponding ester were characterized by GLC-mass spectrometry, PMR spectrometry, and IR spectrophotometry. Each hapten was coupled to bovine serum albumin, and the number of hapten residues per mole of bovine serum albumin was determined by UV spectrophotometric methods. Antibodies to each hapten protein conjugate were developed in rabbits, and titers of the antiserums were checked by evaluating their binding characteristics to tritiated drug.