Clinical and biochemical studies on the gluthathione S-transferases

The glutathione S-transferases (ligandins) are a ubiquitous system of xenobiotic metabolising enzymes. In the rat liver they comprise up to 10% of soluble hepatic protein. Studies in the rat suggested that ligandin was an accurate and sensitive marker of hepatocellular necrosis. and of renal tubular necrosis. The first part of this thesis examines the release of ligandin from liver and kidney in human liver and renal disease in an attempt to determine whether the measurement of ligandin is clinically useful. Ligandin was purified from human liver cytosol using a combination of anion exchange chromatography and gel filtration. The purified protein had similar physicochemical characteristics to ligandin purified by others. The protein was used to raise a monospecific antibody. Ligandin was iodinated by the Chloramine-T method. which yielded a labelled protein of high specific activity. A sensitive and specific radioimmunoassay for human ligandin was developed which had a low intra- and interassay variation. The assay was applied to the study of human liver disease. In acute hepatitis ligandin is released from the liver into serum early in the illness. High serum ligandin levels are seen in the first week of acute hepatitis. The rapid return to normal suggests that ligandin may provide an early indication of recovery. In chronic hepatitis ligandin levels correlated significantly with histological severity of disease. whereas SGOT showed no such correlation. Ligandin may be a better index of severity of disease and for treatment than SGOT. Ligandin was released from the kidney in severe renal ischaemia and in acute tubular necrosis, but was not a reliable predictor or indicator of acute tubular necrosis. Part two examines the distribution of GSH-T activity in organs and in hepatocellular carcinoma. Ligandin was shown to be immunologically similar in all tissues studied. Isoelectric focusing of cytosol separated the three groups of GSH-T activity. Considerable variety in the distribution and activity of GSH-T's was shown in different organs from a single donor, and in the same organs from different donors. Anionic transferase activity was shown to contribute a significant proportion of activity in organs other than the liver. and to be the major source of activity in ovary and lung. In hepatocellular carcinoma cationic GSH-T activity was present in amounts varying from near normal to absent. The anionic and neutral GSH-T's were present in amounts similar to that seen in normal liver. Immunohistochemical studies using a peroxidase-antiperoxidase method showed a rough correlation between tumour differentiation and the amount of ligandin in the tumour

Identifying the Most Significant Microbiological Foodborne Hazards to Public Health: A New Risk Ranking Model

In order to help facilitate a risk-based food safety system, we developed the Foodborne Illness Risk Ranking Model (FIRRM), a decisionmaking tool that quantifies and compares the relative burden to society of 28 foodborne pathogens. FIRRM estimates the annual number of cases, hospitalizations, and fatalities caused by each foodborne pathogen, subsequently estimates the economic costs and QALY losses of these illnesses, and, lastly, attributes these pathogen-specific illnesses and costs to categories of food vehicles, based on outbreak data and expert judgment. The model ranks pathogen-food combinations according to five measures of societal burden. FIRRM incorporates probabilistic uncertainty within a Monte Carlo simulation framework and produces confidence intervals and statistics for all outputs. Gaps in data, most importantly in regards to food attribution and the statistical uncertainty of incidence estimates, currently limit the utility of the model. Once we address these and other problems, however, FIRRM will be a robust and useful decisionmaking tool.foodborne illness, risk ranking, pathogens, health valuation, QALYs, cost of illness, uncertainty, modeling, Monte Carlo

Le souffle poétique

This special issue of JCACS amplifies and intersects multiple themes that challenge our capacity to access air. We invited research presented at the 2019 International Symposium on Poetic Inquiry, as well as new poetic inquiry that engages, plays with, ignites and challenges notions of action in a time of legislated inaction, work that counteracts silencing the breath inside our bones. We looked for oxygen where there was none. The editors of this special issue all use poetry as a form of inquiry in their lives and academic work, and we are delighted to share the work of our colleagues from the poetic inquiry community. We believe that this issue demonstrates the value of using poetic inquiry in academia to highlight the voices of those underrepresented and thus is a vital contribution to the research community.Ce numéro spécial de RACEC amplifie et croise de multiples thèmes qui remettent en question notre capacité à accéder à l'air. Nous avons invité des recherches présentées au Symposium international sur l'enquête poétique 2019, ainsi que des nouvelles enquêtes poétiques qui engagent, jouent avec, enflamment et défient les notions d'action à une époque d'inaction légiférée, un travail qui contrecarre le silence du souffle à l'intérieur de nos os. Nous avons cherché de l'oxygène là où il n'y en avait pas. Les rédacteurs/trices de ce numéro spécial utilisent tous la poésie comme une forme de recherche dans leur vie et leur travail universitaire, et nous sommes ravis de partager le travail de nos collègues de la communauté de recherche poétique. Nous pensons que ce numéro démontre la valeur de l'utilisation de l'enquête poétique dans le monde universitaire pour mettre en lumière les voix de ceux qui sont sous-représentés et constitue donc une contribution essentielle à la communauté des chercheurs

Stable photoinduced metal-organic nanosheet blue phosphor for white light emission

Organic-based phosphors are promising alternatives to rare-earth metal based white light-emitting diodes (LEDs). Integrating phosphors into organic LED systems, however, is constrained by limited long-term chemical- and photo-stability, particularly for blue emitters, along with fabricability. Coumarins are common blue emitters for red-green-blue (RGB) or blue-yellow white light emission (WLE) systems but are susceptible to photodimerization and decay, both supressing fluorescence. This work employs a guest@host architecture to entrap 7-methoxycoumarin (MC) in metal-organic framework nanosheets (MONs) of the 2D phase of ZIF-7 (Z7-NS). This prevented photodimerization due to the arrangement of dye molecules within the nanosheet spacings. Favourably, upon ultraviolet exposure (365 nm), a new intense broader emission band forms irreversibly, derived from charge-transfer behaviour of the MC chromophores. This resulted in intense blue emission with 4.2 × improved photoluminescence quantum yield (PLQY) (Φ = 26.6 %) compared to molecular MC. Contrastingly, encapsulation of MC in 3D ZIF-7 (MC@Z7) also prevented photodimerization, but only exhibited purple-blue low-intensity, low PLQY MC monomeric fluorescence. The fabricability of MC@Z7-NS was demonstrated by inkjet printing blue emitting thin-films that showed improved homogeneity and quantum yield over MC@Z7. Finally, an RGB triple guest@Z7-NS was synthesised and optimised over 30 samples to produce WLE with ideal CIE coordinates of (0.33, 0.34), high PLQY of 65.08 %, and tuneable cool-warm temperatures. Combined, the work demonstrates the remarkable potential of guest@MON systems for improved WLE OLEDs

Hepatocellular carcinoma

Liver cancer is the second leading cause of cancer-related deaths globally and has an incidence of approximately 850,000 new cases per year. Hepatocellular carcinoma (HCC) represents approximately 90% of all cases of primary liver cancer. The main risk factors for developing HCC are well known and include hepatitis B and C virus infection, alcohol intake and ingestion of the fungal metabolite aflatoxin B1. Additional risk factors such as non-alcoholic steatohepatitis are also emerging. Advances in the understanding of the molecular pathogenesis of HCC have led to identification of critical driver mutations; however, the most prevalent of these are not yet druggable targets. The molecular classification of HCC is not established, and the Barcelona Clinic Liver Cancer staging classification is the main clinical algorithm for the stratification of patients according to prognosis and treatment allocation. Surveillance programmes enable the detection of early-stage tumours that are amenable to curative therapies - resection, liver transplantation or local ablation. At more developed stages, only chemoembolization (for intermediate HCC) and sorafenib (for advanced HCC) have shown survival benefits. There are major unmet needs in HCC management that might be addressed through the discovery of new therapies and their combinations for use in the adjuvant setting and for intermediate- and advanced-stage disease. Moreover, biomarkers for therapy stratification, patient-tailored strategies targeting driver mutations and/or activating signalling cascades, and validated measurements of quality of life are needed. Recent failures in the testing of systemic drugs for intermediate and advanced stages have indicated a need to refine trial designs and to define novel approaches

Effect of a major ice storm on understory light conditions in an old-growth Acer-Fagus forest: Pattern of recovery over seven years

We evaluated the effects of a major ice storm on understory light conditions (%PPFD, photosynthetic photon flux density) in an old-growth Acer-Fagus forest in Quebec, based on pre- and post-disturbance light measurements taken until the seventh growing season after the event (which occurred in January 1998). Before the ice storm, most microsites received between 2 and 4%PPFD. Following the ice storm, the stand-level mean %PPFD increased four- to five-fold, ranging from 13.8 to 20.5%PPFD, from 0.3 to 4 m aboveground. Despite its magnitude, the post-ice storm increase in light transmission was short-lived. By 1999 (2-year+), the mean light levels had decreased by half, and recovery to pre-storm conditions occurred within 3-7 years, depending on height. The decrease in light transmission during the post-disturbance years followed an inverse J-shape trend, indicating more dynamic changes early after disturbance. By 2004 (7-year+), light levels at ≤2 m had become slightly but significantly lower than before the ice storm, with most microsites receiving <2%PPFD. The ice storm led to a synchronized increase of the light levels at almost all understory locations, which might allow a high proportion of the advanced regeneration to experience a release. However, due to the rapid recovery of the light conditions to levels similar or lower than before the ice storm, this disturbance should be more advantageous to shade-tolerant species

Bringing Black Feminist's Thoughts, Self-Definitions, and Creative Agency to Digital Media and Technology Design

Users from marginalized groups are often faced with the challenges that result from a lack of diverse thought in the design and implementation of media and technologies that we engage in our daily lives. It is these artifacts that result in the harm, erasure, and hyper-surveillance of Black and Brown people. We seek to disrupt problematic narratives present in tech and design fields by (re)inserting Black Feminism and leveraging our personal experiences to build on design methods. Though research centered on the importance of women’s experiences and standpoints in tech practice is crucial, feminist scholarship has not always reflected the values and the liberation of women who are not white. This paper uses personal narrative to argue for the value of Black feminist thought and methods in the sub-disciplines of computing, such as digital media, human computer interaction (HCI) and human-centered computing (HCC)

Polymyalgia Rheumatica (PMR) Special Interest Group at OMERACT 11: outcomes of importance for patients with PMR

We worked toward developing a core outcome set for clinical research studies in polymyalgia rheumatica (PMR) by conducting (1) patient consultations using modified nominal group technique; (2) a systematic literature review of outcome measures in PMR; (3) a pilot observational study of patients presenting with untreated PMR, and further discussion with patient research partners; and (4) a qualitative focus group study of patients with PMR on the meaning of stiffness, using thematic analysis. (1) Consultations included 104 patients at 4 centers. Symptoms of PMR included pain, stiffness, fatigue, and sleep disturbance. Function, anxiety, and depression were also often mentioned. Participants expressed concerns about diagnostic delay, adverse effects of glucocorticoids, and fear of relapse. (2) In the systematic review, outcome measures previously used for PMR include pain visual analog scores (VAS), morning stiffness, blood markers, function, and quality of life; standardized effect sizes posttreatment were large. (3) Findings from the observational study indicated that asking about symptom severity at 7 AM, or "on waking," appeared more relevant to disease activity than asking about symptom severity "now" (which depended on the time of assessment). (4) Preliminary results were presented from the focus group qualitative study, encompassing broad themes of stiffness, pain, and the effect of PMR on patients' lives. It was concluded that further validation work is required before a core outcome set in PMR can be recommended. Nevertheless, the large standardized effect sizes suggest that pain VAS is likely to be satisfactory as a primary outcome measure for assessing response to initial therapy of PMR. Dissection of between-patient heterogeneity in the subsequent treatment course may require attention to comorbidity as a potential confounding factor