80 research outputs found

    Re St Vincent\u27s Guest House and CUPE, Loc 1082

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    The union alleges that the employer breached the collective agreement between the parties effective January 1, 1989 to December 31, 1990, and in particular art. 13.01, Seniority. The union requests that the grievor be granted the position in question and compensated for any lost income which resulted from the alleged breach

    Simukunin from the Salivary Glands of the Black Fly Simulium vittatum Inhibits Enzymes That Regulate Clotting and Inflammatory Responses

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    BACKGROUND: Black flies (Diptera: Simuliidae) feed on blood, and are important vectors of Onchocerca volvulus, the etiolytic agent of River Blindness. Blood feeding depends on pharmacological properties of saliva, including anticoagulation, but the molecules responsible for this activity have not been well characterized. METHODOLOGY/PRINCIPAL FINDINGS: Two Kunitz family proteins, SV-66 and SV-170, were identified in the sialome of the black fly Simulium vittatum. As Kunitz proteins are inhibitors of serine proteases, we hypothesized that SV-66 and/or -170 were involved in the anticoagulant activity of black fly saliva. Our results indicated that recombinant (r) SV-66 but not rSV-170 inhibited plasma coagulation. Mutational analysis suggested that SV-66 is a canonical BPTI-like inhibitor. Functional assays indicated that rSV66 reduced the activity of ten serine proteases, including several involved in mammalian coagulation. rSV-66 most strongly inhibited the activity of Factor Xa, elastase, and cathepsin G, exhibited lesser inhibitory activity against Factor IXa, Factor XIa, and plasmin, and exhibited no activity against Factor XIIa and thrombin. Surface plasmon resonance studies indicated that rSV-66 bound with highest affinity to elastase (K(D) = 0.4 nM) and to the active site of FXa (K(D) = 3.07 nM). We propose the name "Simukunin" for this novel protein. CONCLUSIONS: We conclude that Simukunin preferentially inhibits Factor Xa. The inhibition of elastase and cathepsin G further suggests this protein may modulate inflammation, which could potentially affect pathogen transmission

    A Three Species Model to Simulate Application of Hyperbaric Oxygen Therapy to Chronic Wounds

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    Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the cost-effectiveness of this therapy

    Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

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    Purpose: Neurofibromatosis type 1 (NF1) is characterized by a highly variable clinical presentation, but almost all NF1-affected adults present with cutaneous and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for the NF1 in-frame deletion, c.2970_2972del (p.Met992del), associated with a mild phenotype without any externally visible tumors. Methods: A total of 135 individuals from 103 unrelated families, all carrying the constitutional NF1 p.Met992del pathogenic variant and clinically assessed using the same standardized phenotypic checklist form, were included in this study. Results: None of the individuals had externally visible plexiform or histopathologically confirmed cutaneous or subcutaneous neurofibromas. We did not identify any complications, such as symptomatic optic pathway gliomas (OPGs) or symptomatic spinal neurofibromas; however, 4.8% of individuals had nonoptic brain tumors, mostly low-grade and asymptomatic, and 38.8% had cognitive impairment/learning disabilities. In an individual with the NF1 constitutional c.2970_2972del and three astrocytomas, we provided proof that all were NF1-associated tumors given loss of heterozygosity at three intragenic NF1 microsatellite markers and c.2970_297

    IFITM3 restricts the morbidity and mortality associated with influenza

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    The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses1, 2, 3, 4, 5, 6, 7. Both the magnitude and breadth of the IFITM proteins’ in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model8, we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 ‘Spanish’ influenza9, 10. Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and human

    Dalhousie University v Dalhousie Staff Assn

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    The Grievor was an administrative secretary with Dalhousie University from September, 1979 to June 1982. During this period, the Grievor\u27s immediate supervisor frequently assigned tasks to the Grievor, and instructed her to perform them by working overtime, if necessary. The Grievor\u27s cumulative record of overtime hours was approved periodically by her supervisor. In December of 1979, a University administrator informed the Grievor\u27s supervisor that future overtime work could be authorized only if the employee agreed to be compensated with paid time off rather than overtime pay. The Grievor was aware of this directive. Her supervisor, however, assured her that she eventually would receive overtime pay for subsequent overtime work. On June 2, 1981, the Grievor was informed by the Vice-President of Administration and Finance that she would be compensated only in the form of paid time off. The Grievor filed a grievance on June 8, in which she claimed overtime pay for 239 1/4 hours, worked between December, 1979 and April 1981. The Employer argued that the extra time worked by the Grievor did not come within the definition of overtime in the Collective Agreement. This definition stated that extra time worked was not overtime unless it was specifically approved in advance by the responsible supervisor . The Employer submitted that the arrangement under which the Grievor performed extra work did not constitute specific approval in advance. Alternatively, the Employer argued that because the grievance was not filed until June 8, 1981, the Grievor could not be compensated for failures to pay overtime in the months of December, 1979 to March 1981 inclusive. In relation to these months, the grievance was filed outside the mandatory time limit in the Collective Agreement. The Union claimed that the Employer was stopped from relying on the time limit

    Re Yarmouth Regional Hospital and CUPE

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    The grievor claims that he was unjustly suspended and denied Union representation. The grievor worked in the housekeeping department at Harbourside Lodge, part of the Employer\u27s hospital. The grievor was interviewed twice on a specific day in relation to the way he conducted himself towards a patient. In the first interview, the grievor and one supervisor were present. In the second, the grievor and two supervisors were present. The grievor asked, at the beginning of the second interview, to be accompanied by his shop steward and he was told by one of the interviewers that there was not time to wait for him and the interview then proceeded without Union representation. Subsequently, the grievor was suspended for two days. The Board was asked to decide these matters as preliminary issues before proceeding with the merits. The Board met on September 24, 1991 and was to meet again on May 27, 1992. On May 21, 1992 the Board was notified that the parties had settled the matter. However, a formal interim award following the hearing on September 24, 1991 was requested

    Re Abbie J Lane Memorial Hospital and Nova Scotia Nurses\u27 Union (NSNU)

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    The Grievor, a registered nurse, Worked at the same hospital as her husband, a psychologist. When she was hired, the Grievor was told that she would not work together with her husband in the same unit. For this reason, the Grievor subsequently refused all temporary postings (floats) to her husband\u27s unit, and her refusal was generally accepted. However, on the day in question, the Grievor was asked to float to the particular unit, and, after repeatedly refusing the assignment, she was suspended, with pay, for the remainder of the day for insubordination. At the hearing, the Union raised a preliminary objection that the Employer was now precluded from arguing just cause because it had maintained throughout the grievance procedure that the matter was not disciplinary. The Board unanimously disposed of the preliminary objection, holding that while the Employer took that position, that was never the view of the Union or the Grievor, and hence, it was not misled in any way. The Union\u27s argument on the main issue was that the Grievor\u27s refusal to obey was based on reasonable grounds, i.e. that it conflicted with her terms of employment. In response, the Employer argued that the order was within the hospital\u27s prerogative to give, that it did not conflict with any earlier order given to the Grievor, and, even if she thought that it did, she should have obeyed the order and then filed a grievance
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