Canada Ltd Research Articles

Canadian Association of Gastroenterology position statement regarding the use of thiopurines for the treatment of inflammatory bowel disease.

Canadian Association of Gastroenterology position statement regarding the use of thiopurines for the treatment of inflammatory bowel disease.

Resting metabolic rate in obese diabetic and obese non-diabetic subjects and its relation to glycaemic control

BackgroundBoth obesity and type II diabetes mellitus are associated with insulin resistance and abnormal metabolic reactions. This study was conducted to evaluate resting metabolic rate in obese diabetic patients and to assess its relation to glycaemic control.ResultsThis is a case control study conducted in Gabir AbuEliz centre in Khartoum, Sudan. A random sample of 40 obese diabetic patients (cases) and 40 obese non-diabetic subjects (controls) were interviewed and examined clinically to exclude presence of acute or chronic medical illness. Haemoglobin A1c was measured for each participant using the “NycoCard Haemoglobin A1c test” (Axis -Shield/ Norway). Fasting blood sugar was measured using one touch(R) glucometer (LifeScan Canada Ltd). The PowerLab 8/35 with a gas analyzer (AD Instruments, Castle Hill Australia) was used for measurement of VO2, VCO2 and Respiratory exchange ratio (RER). Resting metabolic rate was calculated using the Weir equation. VO2 (mean+/-SD) ml/min was significantly higher among cases (209.9+/-42.7) compared to the controls (192.4+/-28.1), (P = 0.034). Similarly, VCO2 (mean+/-SD) ml/min was higher among cases (191.4+/-35.0) than controls (178.3+/-22.5), (P = 0.05). Resting metabolic rate “RMR” (mean+/-SD) kcal/day was higher in obese diabetic patients (1480.7 +/- 274.2) than obese non-diabetic subjects (1362.4+/- 184.8), (P = 0.027). Participants with high glycated haemoglobin had higher RMR than those with normal glycated haemoglobin (P = 0.016).ConclusionIt is concluded that resting metabolic rate is significantly higher in obese diabetic patients compared to obese non-diabetics, especially in those with poor glycaemic control.

Recovery for Psychiatric Injury in Canada: A Tale of Two Cases

Mustapha v. Culligan of Canada Ltd [2008] 2 SCR 114 was the Supreme Court of Canada’s first opportunity for more than 50 years to restate the principles of liability for psychiatric injury as applied in Canada. However, McLachlin CJ’s economically worded judgment did not go into the issues in any detail. In the recent case of Healey v. Lakeridge Health Corp 2011 ONCA 55, the Ontario Court of Appeal had to resolve an ambiguity in McLachlin CJ’s judgment: the plaintiffs argued that it had lowered the recognisable psychiatric illness threshold, but the Ontario Court of Appeal upheld the orthodox view. Healey, however, affirms another distinctive trend seemingly initiated by Mustapha: to treat issues of psychiatric injury under the heading of remoteness rather than duty.

StemCells, Inc.: Clinical Trials of Stem Cell Therapies for Cns Disorders

Martin McGlynn, President & Chief Executive Officer of StemCells, Inc., talks to Regenerative Medicine about the company's ongoing clinical trials with their human neural stem cell treatment (HuCNS-SC). Martin McGlynn joined StemCells, Inc. in January of 2001 as President and Chief Executive Officer, and was elected to its Board of Directors on February 6, 2001. Martin McGlynn has spent several decades as a senior executive in the life sciences industry in Europe, Canada and the USA. He began his career in Manufacturing Operations with Becton Dickinson, Ireland Ltd. then joined Abbott Labs in 1977 where he held positions as General Manager, Abbott Ireland Ltd, President and General Manager of Abbott Canada Ltd and Vice President of Abbott International Ltd. Martin McGlynn currently serves as a member of the Board of the Alliance for Regenerative Medicine and is co-Chairman of its Operations and Governance Committee.

Comment on “QA procedures in radiation therapy are outdated and negatively impact the reduction of errors” [Med. Phys. 38, 5835 (2011)

To the Editor, In the November 2011 Point/Counter Point debate, both authors referred to the incident in Tyler TX as events where “QA procedures were not followed” or where “horrific medical physics errors occurred.”1 As the physicist of record in Tyler at the time of the Therac 25 Malfunction 54, I would like to clarify the record regarding this event. In contrast to the statements made by the authors, Malfunction 54 was not the result of a medical physicist error or failure to perform QA. The incident was the result of a well documented software error that permitted theTherac 25 linac to operate in photon mode without a target or flattening filter in the beam, resulting in a near-instantaneous dose of ∼16 000 cGy. There was no warning for the therapist and very little information from the Therac 25 that it had delivered such a high dose; the Malfunction 54 code was a general indicator that either too high or too low a dose had been delivered. As one of the first digitally operated linacs, spurious malfunction codes occurred periodically; the manufacturer [Atomic Energy of Canada Ltd (AECL)] indicated these were due to machine noise and that there were no actual problems. Following the first event, three AECL engineers examined the Therac 25 and could find no problems. At the time of the second incident, the therapist was teaching a student and recalled changing the mode on the Therac 25 from photons to electrons. With her recall of the keystrokes used for the patient, we were able to reproduce the Malfunction 54. These instructions were subsequently used to reproduce the Malfunction 54 type event at all Therac 25 locations. There was a similar Therac 25 error in Yakima, Washington resulting from a different series of events—toggling from light field to treatment mode caused the target to be left out—that also resulted in a patient death. The Therac 25 errors have been described in detail,2 were the result of manufacturer software deficiencies, and had nothing to do with the lack of a qualified medical physicist or attention to QA. Additional details on the Therac 25 and other linac accidents will be described in an upcoming review article for Medical Physics.

Rothmans sees market share slip

PurposeThe purpose of this paper is to examine the factors contributing to the historic loss of market share experienced by Rothmans Benson & Hedges (RBH), Canada's second largest tobacco firm.Design/methodology/approachThe paper presents a case study of the marketing of RBH flagship cigarette brand Rothmans between 1957 and 2000, comparing its performance with brands owned by market leader Imperial Tobacco Canada Ltd (ITL).FindingsSometimes it is no fun at all being a marketer. You have a generous advertising budget, follow the rules of strategic brand management, make sure your brand communications are consistent with the historical brand identity – and yet your market share declines. Take the case of RBH – historically Canada's second‐largest seller of cigarettes – which saw its market share slide from 43 percent in 1975 to a mere 17 percent by the mid‐1990s. It does not help of course if the government decides to introduce regulations restricting where and how you can advertise, but other tobacco firms seemed to adapt more successfully, gaining ground in key consumer segments. What went wrong for Rothmans?Practical implicationsThe paper highlights the importance of contemporary references and imagery in enabling a brand to keep pace with changes in the target market.Social implicationsThe paper shows how legislation intended to restrict product advertising can have unintended consequences as firms use creative marketing to exploit loopholes in regulation.Originality/valueThe paper draws on internal corporate documents made public through tobacco industry legal challenges to Canada's Tobacco Products Control Act (TPCA), in addition to trade press and promotional material.

Cost Effectiveness of Infant Vaccination for Rotavirus in Canada

Rotavirus is the main cause of gastroenteritis in Canadian children younger than five years of age, resulting in significant morbidity and cost. The present study provides evidence on the cost effectiveness of two alternative rotavirus vaccinations (RotaTeq [Merck Frosst Canada Ltd, Canada] and Rotarix [GlaxoSmithKline, Canada]) available in Canada. Analysis was conducted through a Markov model that followed a cohort of children from birth to five years of age. Analysis used pertinent data on the natural history of rotavirus and the effects of vaccination. Estimates of heath care costs for children requiring hospitalizations and emergency department visits were derived from the Canadian Immunization Monitoring Program, Active (IMPACT) surveillance, emergency department studies, as well as other Canadian studies. The model estimated the effect of vaccination on costs and quality-adjusted life years (QALYs). The incremental cost per QALY gained from the health care system perspective was $122,000 for RotaTeq and $108,000 for Rotarix. From the societal perspective, both vaccination strategies were dominant - both cost saving and more effective. The cost-effectiveness of vaccination is dependent on the mode of administration, the perspective adopted and the cost of the vaccine. From a societal perspective, a universal vaccination program against rotavirus will be both cost saving and more effective than no vaccination. Becasue the majority of rotavirus infections do not require emergency department visits or hospital admission, from a health care system perspective, a program would not be considered cost effective.

Assessing patient report of function: content validity of the Functional Performance Inventory-Short Form (FPI-SF) in patients with chronic obstructive pulmonary disease (COPD)

PurposeThe performance of daily activities is a major challenge for people with chronic obstructive pulmonary disease (COPD). The Functional Performance Inventory (FPI) was developed based on an analytical framework of functional status and qualitative interviews with COPD patients describing these difficulties. The 65-item FPI was reduced to a 32-item short form (SF) through a systematic process of qualitative and quantitative item reduction and formatted for greater clarity and ease of use. This study examined the content validity of the reduced, reformatted form of the instrument, the FPI-SF.Patients and methodsQualitative cognitive interviews were conducted with COPD patients recruited from three geographically diverse pulmonary clinics in the United States. Interviews were designed to assess respondent interpretation of the instrument, evaluate clarity and ease of completion, and identify any new activities participants found important and difficult to perform that were not represented by the existing items.ResultsTwenty subjects comprised the sample; 12 (60%) were male, 14 (70%) were Caucasian, the mean age was 63.0 ± 11.3 years, 12 (60%) were retired, the mean forced expiratory volume in 1 second (FEV1) was 1.5 ± 0.5 L, and the mean percent predicted FEV1 was 48.4% ± 13.1%. Participants understood the FPI-SF as intended, including instructions, items, and response options. Two minor formatting changes were suggested to improve clarity of presentation. Participants found the content of the FPI-SF to be comprehensive, with items covering activities they felt were important and often difficult to perform.ConclusionThese results, together with its development history and previously tested quantitative properties, suggest that the FPI-SF is content valid for use in clinical studies of COPD.

Effects of exposure to oil sands process-affected water from experimental reclamation ponds on Chironomus dilutus

Effective detoxification of oil sands process-affected water (OSPW) is one issue associated with bitumen extraction in the Alberta oil sands. It has been suggested that reclamation ponds can be used to passively treat OSPW, potentially allowing for its safe return to the environment. In this study, OSPW was sampled in two batches (A and B) from the Syncrude Canada Ltd. West In-Pit (WIP) settling pond and from three experimental reclamation ponds – Big Pit, FE5, and TPW. Acute (10 d) and chronic (until adult emergence) exposures of Chironomus dilutus larvae to OSPW were conducted and survival, growth, development, and behavior were assessed. Masses of larvae exposed to WIP-OSPW were 64–77% less than the freshwater control (p < 0.001). Similarly, chronic exposure to WIP-OSPW resulted in significantly (p < 0.05) less pupation than in the freshwater control, with 31% (A) and 71% (B) less pupation of larvae exposed to WIP-OSPW. Rates of emergence were significantly less for larvae exposed to WIP-OSPW, with only 13% (A) and 8% (B) of larvae emerging as adults when exposed to WIP-OSPW, compared to 81% in the freshwater control (p < 0.0001). Pupation and emergence rates were significantly less in TPW than freshwater control (p < 0.05), but there were no differences observed in Big Pit or FE5. Lesser toxicity was observed in reclaimed OSPW compared to fresh OSPW and this coincided with lesser concentrations of NAs. The results presented are consistent with the hypothesis that an organic fraction is the cause of the toxicity of OSPW toward C. dilutus and that OSPW aged in reclamation ponds retains toxicity and therefore, more aggressive, targeted treatment of OSPW is required to accelerate decreases.

&lt;i&gt;Fullowka v. Pinkerton’s of Canada Ltd.&lt;/i&gt; and the Material Contribution Test for Factual Causation in Negligence

On 18 February 2010 the Supreme Court of Canada released its judgment in Fullowka v. Pinkerton’s of Canada Ltd. In a unanimous decision, the Court canvassed issues including duty and standard of care, factual causation, and the vicarious liability of unions, focusing especially upon duty and standard of care. This case comment examines, in particular, the decision’s treatment of factual causation in negligence.

Hyperphosphorylation by Cyclin B/CDK1 in Mitosis Resets CUX1 DNA Binding Clock at Each Cell Cycle*

The p110 CUX1 homeodomain protein participates in the activation of DNA replication genes in part by increasing the affinity of E2F factors for the promoters of these genes. CUX1 expression is very weak in quiescent cells and increases during G(1). Biochemical activities associated with transcriptional activation by CUX1 are potentiated by post-translational modifications in late G(1), notably a proteolytic processing event that generates p110 CUX1. Constitutive expression of p110 CUX1, as observed in some transformed cells, leads to accelerated entry into the S phase. In this study, we investigated the post-translation regulation of CUX1 during mitosis and the early G(1) phases of proliferating cells. We observed a major electrophoretic mobility shift and a complete inhibition of DNA binding during mitosis. We show that cyclin B/CDK1 interacts with CUX1 and phosphorylates it at multiple sites. Serine to alanine replacement mutations at 10 SP dipeptide sites were required to restore DNA binding in mitosis. Passage into G(1) was associated with the degradation of some p110 CUX1 proteins, and the remaining proteins were gradually dephosphorylated. Indirect immunofluorescence and subfractionation assays using a phospho-specific antibody showed that most of the phosphorylated protein remained in the cytoplasm, whereas the dephosphorylated protein was preferentially located in the nucleus. Globally, our results indicate that the hyperphosphorylation of CUX1 by cyclin B/CDK1 inhibits its DNA binding activity in mitosis and interferes with its nuclear localization following cell division and formation of the nuclear membrane, whereas dephosphorylation and de novo synthesis contribute to gradually restore CUX1 expression and activity in G(1).

Field performance of alder- Frankia symbionts for the reclamation of oil sands sites

The Canadian province of Alberta is the world's largest producer of petroleum products from oil sands exploitation. Oil sands process-affected materials (OSPM), such as tailings sand, produced as a result of bitumen extraction, has low fertility, low organic matter content, it is alkaline, compactable, and contains residual hydrocarbons, making it a very inhospitable growth environment. The petroleum industry is currently involved in efforts to revegetate and remediate the tailings sand. One approach used is revegetation of the reclamation sites with Frankia-inoculated alders. Alders are primary succession trees that have the ability to grow in nutrient poor and waterlogged environments, in part because they form a symbiotic relationship with the nitrogen-fixing Actinobacteria, Frankia. In 2005, field trials were established at Syncrude Canada Ltd. The effect of Frankia-inoculated alders on soil quality was evaluated by monitoring the chemical and microbiological characteristics of the soil. The impact on the indigenous microbial community was also studied using hydrocarbon mineralization assays, and molecular approaches, such as denaturing gradient gel electrophoresis (DGGE). Plant parameters (biomass, nitrogen content) were measured to evaluate the impact of Frankia on alder health and growth. After two growth seasons, Frankia-inoculated and non-inoculated alders yielded comparable amounts of plant biomass and there was an increase in hydrocarbon (hexadecane, naphthalene and phenanthrene) mineralization where the reclamation site had been planted with alder- Frankia. The alder rhizosphere samples all had comparable hydrocarbon mineralization rates. DGGE profiles confirmed a change in the microbial communities of the bulk soil between unplanted and alder- Frankia treatments. Soil tests showed that alder- Frankia decreased soil pH (from 7.5 to 6.6, in 2006, and from 8.2 to 7.2 in 2007) and plant-available sodium content (70% reduction), and had a positive impact on soil organic matter content (increase in up to 6 times in alder- Frankia plots). The field results have confirmed that the alder- Frankia combination results in improved remediation capabilities and enhances soil quality. These improvements in soil quality of the reclamation site provide evidence of the potential of alder- Frankia symbionts to be part of a reclamation strategy for the reforestation of the site, and the re-establishment of a balanced ecosystem.

Case Law

Belgium – Constitutional Court ruling on nuclear taxes (2010) Brazil – Federal Court ruling on partial licence for works at Angra III (2009) Canada – Federal Court decision respecting intellectual property and trade mark infringement action: Atomic Energy of Canada Ltd. v Areva NP Canada Ltd (2009) United States – Judgement of a U.S. Court of Appeals on consideration of the environmental impacts of the risk of spent fuel pool fires (2009) Judgement of a U.S. Court of Appeals on a licence to perform in situ leach uranium mining (2010)

English

The objective of reclamation of surface mined lands in the Athabasca Oil Sands Region in northern Alberta is to return the land to an equivalent land capability. The native soils disturbed by surface mining must be salvaged and replaced during reclamation in accordance with the current provincial legislation, consequently, the topsoil (LFH or Ah, Ahe, Ae, Oa, Oi, Oe horizons) and subsoil (B and C horizons) or upper two meters of organic soil are removed and stockpiled during overburden and resource extraction activities and are replaced over tailings sand or overburden during reclamation. The objective of this research was to assess the carbon (C) balance within the reclaimed landscape by monitoring the soil, biomass and dead organic matter carbon pools from the time of initial reclamation forward at the operations of Syncrude Canada Ltd. To achieve this objective C losses and gains were monitored through respiration and biometric assessments, respectively. These methods were then used to evaluate the C dynamics of various reclamation strategies and soil prescriptions compared to targeted natural undisturbed ecosites. Net C accumulation was determined using biometric measurement techniques for three years at several long-term- monitoring sites representing six soil cover prescriptions and three of the most common natural soil types. Measurements of the annual production of above and below ground C biomass and soil respiration were used to develop biometric estimates of net ecosystem productivity. The soil component comprised a substantially larger proportion of the total C pools in the reclaimed areas. The soil C pool was larger for all reconstructed sites with a peat-mix or LFH cap than for the natural sites, especially sites with mature tree stands 70 years of age or greater which had substantially more C stored in the above ground biomass than in the soil. Measurement of inputs to and output (losses) from the total C pool for reclaimed sites with different soil covers indicated that losses were nearly balanced by inputs in the early years following revegetation.

Judicial Regulation of the Legal Profession: Correspondent's Report from Canada

The substance and import of the Supreme Court's decisions R v Cunningham and Fullowka v Pinkerton's of Canada Ltd for the ethical and legal obligations of Canadian lawyers are discussed. The challenges and opportunities that the intervention of the Court into the regulation of the legal profession present are highlighted.

Knowledge management initiatives in the Canadian nuclear industry

The Canadian nuclear industry has been faced with many challenges in the area of Knowledge Management (KM) over the past decade. Increasing levels of retirement have come at a time when the industry is facing increased demand for experienced nuclear scientists and engineers for refurbishment, decommissioning and new builds. In the mid-1990s, the industry was faced with the prospect of a growing shortage of specialist skills and the loss of important technical knowledge and experience. The recognition of the importance of the problem and the need to act prompted the Canadian nuclear utilities, Atomic Energy Canada Ltd (AECL) and the CANDU Owner's Group (COG), to undertake several proactive measures to address the problem. This paper outlines several of their initiatives that have helped to address these challenges.

Regulation of the Met Receptor-tyrosine Kinase by the Protein-tyrosine Phosphatase 1B and T-cell Phosphatase

The non-receptor protein-tyrosine phosphatases (PTPs) 1B and T-cell phosphatase (TCPTP) have been implicated as negative regulators of multiple signaling pathways including receptor-tyrosine kinases. We have identified PTP1B and TCPTP as negative regulators of the hepatocyte growth factor receptor, the Met receptor-tyrosine kinase. In vivo, loss of PTP1B or TCPTP enhances hepatocyte growth factor-mediated phosphorylation of Met. Using substrate trapping mutants of PTP1B or TCPTP, we have demonstrated that both phosphatases interact with Met and that these interactions require phosphorylation of twin tyrosines (Tyr-1234/1235) in the activation loop of the Met kinase domain. Using confocal microscopy, we show that trapping mutants of both PTP1B and the endoplasmic reticulum-targeted TCPTP isoform, TC48, colocalize with Met and that activation of Met enables the nuclear-localized isoform of TCPTP, TC45, to exit the nucleus. Using small interfering RNA against PTP1B and TCPTP, we demonstrate that phosphorylation of Tyr-1234/1235 in the activation loop of the Met receptor is elevated in the absence of either PTP1B or TCPTP and further elevated upon loss of both phosphatases. This enhanced phosphorylation of Met corresponds to enhanced biological activity and cellular invasion. Our data demonstrate that PTP1B and TCPTP play distinct and non-redundant roles in the regulation of the Met receptor-tyrosine kinase.

Exacerbation of depression associated with starting raltegravir: a report of four cases

Exacerbation of depression associated with starting raltegravir: a report of four cases

CA1 ECONOMIC ANALYSIS OF IMPLANTABLE CARDIOVERTER DEFIBRILLATORS INTHE PRIMARY PREVENTION OF SUDDEN CARDIAC DEATH—A CANADIAN PERSPECTIVE

CA1 ECONOMIC ANALYSIS OF IMPLANTABLE CARDIOVERTER DEFIBRILLATORS INTHE PRIMARY PREVENTION OF SUDDEN CARDIAC DEATH—A CANADIAN PERSPECTIVE Deniz B, Sadri H United BioSource Corporation, Concord, MA, USA, Medtronic of Canada Ltd,Toronto, ON, Canada OBJECTIVE: To conduct a cost-benefit analysis (CB) for the Implantable Cardioverter Defibrillators (ICDs) in the primary prevention of Sudden Cardiac Death (SCD) compared to amiodarone.METHODS: A discrete event simulation model was built to determine the cost-benefit ratio associated with ICDs from a societal perspective in Canada using the “value of life” approach as a measure of “benefit”. The clinical inputs were derived from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) and the Amiodarone Trial Analysis (ATMA) studies. The related costs were derived from the Ontario Health Insuranace Plans’ (OHIP) schedule of benefits and fees, Ontario Drug Benefit formulary (ODB) and published data. The value of life in Canada (CND$5.8Mil.), as determined by Health Canada, was used in the model. One hundred replicaitons of 1000 identical twin pairs over 7 years, aligned with the average life of an ICD, were run. The costs (year 2006) and outcomes ere discounted at 3%. Sensitivity Analysis (SAs) were performed for key input parameters. RESULTS: The absolute all-cause mortality was reduced by eight percent with ICD over seven years compared to amiodarone. The average costs associated with ICD and amiodarone treatments were estimated as CND$32,000 and CND$6400 per patient, respectively. The predicted cost-benefit ratio (CBR) was 0.04. This figure suggests that for every $1 spent for ICD in the primary prevention of SCD the society will gain $25 in “value” by human lives saved. SAs showed that results were robust (CBR: 0.035–0.044). CONCLUSION: IDs reduce the risk of SCD due to arrhythmia compared to amiodarone. The estimated CBR suggests that ICDs are worthwhile investment from a societal perspective in Canada. The initial investment for ICD in primary prevention of SCD in Canada is comparable and in many cases lower when compared to other societal programs for saving lives.

Growing season energy and water exchange from an oil sands overburden reclamation soil cover, Fort McMurray, Alberta, Canada

AbstractThe oil sands mining industry in Canada is required to return mining areas to a land capability equivalent to that which existed prior to mining. During the reclamation process, ecosystems are created that bear little similarity to boreal forests that existed prior to mining. Quantifying the water balance of reclaimed ecosystems is critical in establishing whether there is sufficient moisture for vegetation growth and in the fate of salts, which can be toxic when drawn to the surface or leached out of the covers. At Syncrude Canada Ltd's Mildred Lake mine north of Fort McMurray, Alberta, the surface energy balance was measured atop a reclaimed saline‐sodic overburden pile during three growing seasons using eddy covariance. At the onset of the study, the dominant vegetation was foxtail barley, which changed to sweet clover in 2004, and a low‐density species mix in 2005, including some aspen and white spruce seedlings. The 2005 growing season was cooler and wetter than 2003 and 2004, and there were seasonal differences in the delivery of precipitation among years. There were distinct differences in the surface energy balance among the study years related to weather, soil moisture, vegetation and stage of growth. Latent heat was the largest consumer of energy in 2003, and mid‐day fluxes of sensible and latent heat were approximately equal. In 2004, sensible heat became the dominant flux, primarily due to prolonged dry periods, whereas the wet 2005 season had the greatest latent heat flux density of any year. Ground heat flux declined throughout the growing season and ranged between 3 and 17% of net radiation. Total evapotranspiration was 246, 224 and 283 mm for 2003, 2004 and 2005, respectively. A total derivative analysis of the Penman‐Monteith equation reveals the influence of available energy, vapour pressure deficit and surface conductance in controlling evapotranspiration. Copyright © 2008 John Wiley &amp; Sons, Ltd.