283 research outputs found

    An analysis of some problems in teaching dramatic literature with specific application to Julius Caesar.

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    Thesis (Ed.M.)--Boston UniversityThe problem is threefold: (1) to review professional literature to determine the place of dramatic literature in the language arts program, (2) to review the methods of teaching dramatic literature, and (3) to prepare a source unit which might serve as a guide for the teaching of Julius Caesar according to current professional thought. The writer assumed his research of professional information would indicate the most effective ways to promote understanding and appreciation of dramatic literature. As a language arts teacher, he felt the need for this study. [TRUNCATED

    Group Supervision Attitudes: Supervisory Practices Fostering Resistance to Adoption of Evidence-Based Practices

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    The focus of this study was to qualitatively evaluate worker’s attitudes about clinical supervision. It is believed that poor attitudes toward clinical supervision can create barriers during supervision sessions. Fifty-one participants within a social services organization completed an open-ended questionnaire regarding their clinical supervision experiences. Results suggest four key areas which appear to be strong factors in workers’ experiences and attitudes regarding group supervision: a. facilitator’s skill level; b. creativity; c. utilization of technology; and d. applicability. For organizations interested in overcoming potential barriers to adopting best practices, effectively addressing workers’ negative attitudes toward group supervision would be a worthy endeavor

    Acute Liver Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

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    CONTEXT Develop evidence-based criteria for individual organ dysfunction. OBJECTIVES Evaluate current evidence and develop contemporary consensus criteria for acute liver dysfunction with associated outcomes in critically ill children. DATA SOURCES Electronic searches of PubMed and Embase conducted from January 1992 to January 2020, used medical subject heading terms and text words to characterize acute liver dysfunction and outcomes. STUDY SELECTION Studies evaluating critically ill children with acute liver dysfunction, assessed screening tools, and outcomes were included. Studies evaluating adults, infants ≤36 weeks gestational age, or animals or were reviews/commentaries, case series with sample size ≤10, or non-English language studies were excluded. DATA EXTRACTION Data were abstracted from each eligible study into a data extraction form along with risk of bias assessment by a task force member. RESULTS The systematic review supports criteria for acute liver dysfunction, in the absence of known chronic liver disease, as having onset of symptoms <8 weeks, combined with biochemical evidence of acute liver injury, and liver-based coagulopathy, with hepatic encephalopathy required for an international normalized ratio between 1.5 and 2.0. LIMITATIONS Unable to assess acute-on-chronic liver dysfunction, subjective nature of hepatic encephalopathy, relevant articles missed by reviewers. CONCLUSIONS Proposed criteria identify an infant, child, or adolescent who has reached a clinical threshold where any of the 3 outcomes (alive with native liver, death, or liver transplant) are possible and should prompt an urgent liaison with a recognized pediatric liver transplant center if liver failure is the principal driver of multiple organ dysfunction

    The role of immunosuppression in long-term graft hepatitis and fibrosis after paediatric liver transplant comparison of two treatment protocols:comparison of two treatment protocols

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    Background and aims: We have previously demonstrated high rates of chronic allograft hepatitis and fibrosis in liver transplant patients on long-term cyclosporine monotherapy. We subsequently changed practice to add low-dose prednisolone to maintenance treatment with tacrolimus post-transplant. The aim of the study was to assess the impact of the immunosuppression change on graft histopathology.Methods: Patients treated in this era (Tac + Pred, 2000–2009, N = 128) were compared to a historical cohort, who had been maintained on a steroid-free, cyclosporine-based regime (CSA-Only, 1985–1996, N = 129). Protocol liver biopsies and laboratory tests were performed five- and ten-years post-transplant in both groups.Results: Compared to CSA-Only, the Tac + Pred cohort had significantly lower rates of chronic hepatitis (CH) at five (20% vs. 44%, p Conclusion: Increased immunosuppression effectively reduced chronic allograft hepatitis and fibrosis at five years, suggesting it is an immunologically driven variant of rejection. However, there was no significant reduction in the degree of fibrosis at ten years, indicating a multifactorial origin for long term graft fibrosis

    MR spectroscopy-based brain metabolite profiling in propionic acidaemia: metabolic changes in the basal ganglia during acute decompensation and effect of liver transplantation

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    Background: Propionic acidaemia (PA) results from deficiency of Propionyl CoA carboxylase, the commonest form presenting in the neonatal period. Despite best current management, PA is associated with severe neurological sequelae, in particular movement disorders resulting from basal ganglia infarction, although the pathogenesis remains poorly understood. The role of liver transplantation remains controversial but may confer some neuro-protection. The present study utilises quantitative magnetic resonance spectroscopy (MRS) to investigate brain metabolite alterations in propionic acidaemia during metabolic stability and acute encephalopathic episodes.Methods: Quantitative MRS was used to evaluate brain metabolites in eight children with neonatal onset propionic acidaemia, with six elective studies acquired during metabolic stability and five studies during acute encephalopathic episodes. MRS studies were acquired concurrently with clinically indicated MR imaging studies at 1.5 Tesla. LCModel software was used to provide metabolite quantification. Comparison was made with a dataset of MRS metabolite concentrations from a cohort of children with normal appearing MR imaging.Results: MRI findings confirm the vulnerability of basal ganglia to infarction during acute encephalopathy. We identified statistically significant decreases in basal ganglia glutamate+glutamine and N-Acetylaspartate, and increase in lactate, during encephalopathic episodes. In white matter lactate was significantly elevated but other metabolites not significantly altered. Metabolite data from two children who had received liver transplantation were not significantly different from the comparator group.Conclusions: The metabolite alterations seen in propionic acidaemia in the basal ganglia during acute encephalopathy reflect loss of viable neurons, and a switch to anaerobic respiration. The decrease in glutamine + glutamate supports the hypothesis that they are consumed to replenish a compromised Krebs cycle and that this is a marker of compromised aerobic respiration within brain tissue. Thus there is a need for improved brain protective strategies during acute metabolic decompensations. MRS provides a non-invasive tool for which could be employed to evaluate novel treatments aimed at restoring basal ganglia homeostasis. The results from the liver transplantation sub-group supports the hypothesis that liver transplantation provides systemic metabolic stability by providing a hepatic pool of functional propionyl CoA carboxylase, thus preventing further acute decompensations which are associated with the risk of brain infarction

    Investigation of the molecular profile of basal cell carcinoma using whole genome microarrays

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    BACKGROUND: Skin cancer accounts for 1/3 of all newly diagnosed cancer. Although seldom fatal, basal cell carcinoma (BCC) is associated with severe disfigurement and morbidity. BCC has a unique interest for researchers, as although it is often locally invasive, it rarely metastasises. This paper, reporting the first whole genome expression microarray analysis of skin cancer, aimed to investigate the molecular profile of BCC in comparison to non-cancerous skin biopsies. RNA from BCC and normal skin specimens was analysed using Affymetrix whole genome microarrays. A Welch t-test was applied to data normalised using dCHIP to identify significant differentially-expressed genes between BCC and normal specimens. Principal component analysis and support vector machine analysis were performed on resulting genelists, Genmapp was used to identify pathways affected, and GOstat aided identification of areas of gene ontology more highly represented on these lists than would be expected by chance. RESULTS: Following normalisation, specimens clustered into groups of BCC specimens and of normal skin specimens. Of the 54,675 gene transcripts/variants analysed, 3,921 were differentially expressed between BCC and normal skin specimens. Of these, 2,108 were significantly up-regulated and 1,813 were statistically significantly down-regulated in BCCs. CONCLUSION: Functional gene sets differentially expressed include those involved in transcription, proliferation, cell motility, apoptosis and metabolism. As expected, members of the Wnt and hedgehog pathways were found to be significantly different between BCC and normal specimens, as were many previously undescribed changes in gene expression between normal and BCC specimens, including basonuclin2 and mrp9. Quantitative-PCR analysis confirmed our microarray results, identifying novel potential biomarkers for BCC

    A Unified Account of the Moral Standing to Blame

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    Recently, philosophers have turned their attention to the question, not when a given agent is blameworthy for what she does, but when a further agent has the moral standing to blame her for what she does. Philosophers have proposed at least four conditions on having “moral standing”: 1. One’s blame would not be “hypocritical”. 2. One is not oneself “involved in” the target agent’s wrongdoing. 3. One must be warranted in believing that the target is indeed blameworthy for the wrongdoing. 4. The target’s wrongdoing must some of “one’s business”. These conditions are often proposed as both conditions on one and the same thing, and as marking fundamentally different ways of “losing standing.” Here I call these claims into question. First, I claim that conditions (3) and (4) are simply conditions on different things than are conditions (1) and (2). Second, I argue that condition (2) reduces to condition (1): when “involvement” removes someone’s standing to blame, it does so only by indicating something further about that agent, viz., that he or she lacks commitment to the values that condemn the wrongdoer’s action. The result: after we clarify the nature of the non-hypocrisy condition, we will have a unified account of moral standing to blame. Issues also discussed: whether standing can ever be regained, the relationship between standing and our "moral fragility", the difference between mere inconsistency and hypocrisy, and whether a condition of standing might be derived from deeper facts about the "equality of persons"

    Immune Status in Children Before Liver Transplantation—A Cross-Sectional Analysis Within the ChilsSFree Multicentre Cohort Study

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    Background: Both, markers of cellular immunity and serum cytokines have been proposed as potential biomarkers for graft rejection after liver transplantation. However, no good prognostic model is available for the prediction of acute cellular rejection. The impact of underlying disease and demographic factors on immune status before pediatric liver transplantation (pLTx) is still poorly understood. We investigated expression of immune markers before pLTx, in order to better understand the pre-transplant immune status. Improved knowledge of the impact of pre-transplant variables may enhance our understanding of immunological changes post pLTx in the future.Methods: This is a cross-sectional analysis of data from the ChilSFree study, a European multicentre cohort study investigating the longitudinal patterns of immune response before and after pLTx. Immune cell counts and soluble immune markers were measured in 155 children 1–30 days before pLTx by TruCount analysis and BioPlex assays. Results were logarithmised due to skewed distributions and then compared according to age, sex, and diagnosis using t-tests, ANOVAs, and Tukey post-hoc tests. The association between immune markers at time of pLTx and patients' age was assessed using a fractional polynomial approach. Multivariable regression models were used to assess the relative contribution of each factor.Results: Sex had no effect on immune status. We found strong evidence for age-specific differences in the immune status. The majority of immune markers decreased in a log-linear way with increasing age. T and B cells showed a sharp increase within the first months of life followed by a log-linear decline in older age groups. Several immune markers were strongly associated with underlying diagnoses. The effects of age and underlying disease remained virtually unchanged when adjusting for each other in multivariable models.Discussion: We show for the first time that age and diagnosis are major independent determinants of cellular and soluble immune marker levels in children with end-stage liver disease. These results need to be considered for future research on predictive immune monitoring after pLTx

    Biallelic mutations in NBAS cause recurrent acute liver failure with onset in infancy

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    Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency. Few conditions are known to cause recurrent acute liver failure (RALF), and in about 50% of cases, the underlying molecular cause remains unresolved. Exome sequencing in five unrelated individuals with fever-dependent RALF revealed biallelic mutations in NBAS. Subsequent Sanger sequencing of NBAS in 15 additional unrelated individuals with RALF or ALF identified compound heterozygous mutations in an additional six individuals from five families. Immunoblot analysis of mutant fibroblasts showed reduced protein levels of NBAS and its proposed interaction partner p31, both involved in retrograde transport between endoplasmic reticulum and Golgi. We recommend NBAS analysis in individuals with acute infantile liver failure, especially if triggered by fever

    UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care

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    The risks of poor transition include delayed and inappropriate transfer that can result in disengagement with healthcare. Structured transition care can improve control of chronic digestive diseases and long-term health-related outcomes. These are the first nationally developed guidelines on the transition of adolescent and young persons (AYP) with chronic digestive diseases from paediatric to adult care. They were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology under the auspices of the Adolescent and Young Persons (A&YP) Section. Electronic searches for English-language articles were performed with keywords relating to digestive system diseases and transition to adult care in the Medline (via Ovid), PsycInfo (via Ovid), Web of Science and CINAHL databases for studies published from 1980 to September 2014. The quality of evidence and grading of recommendations was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The limited number of studies in gastroenterology and hepatology required the addition of relevant studies from other chronic diseases to be included. These guidelines deal specifically with the transition of AYP living with a diagnosis of chronic digestive disease and/or liver disease from paediatric to adult healthcare under the following headings; 1. Patient populations involved in AYP transition 2. Risks of failing transition or poor transition 3. Models of AYP transition 4. Patient and carer/parent perspective in AYP transition 5. Surgical perspectiv
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