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This article discusses the implementation and evaluation of a simulation-based teaching competition called SimStars. The competition aimed to recruit and retain new clinician educators to the faculty by utilizing motivational theory and the power of competition. The competition consisted of online workshops and a competition phase where teams designed and presented their own simulation scenarios. The evaluation of the competition showed a strong interest in simulation-based teaching and a desire to design future scenarios. The article emphasizes the importance of faculty development and the potential of competition to promote simulation-based teaching across hospitals. [Extracted from the article]

Background: Abnormalities in serum potassium are a well known complication of chronic kidney disease (CKD), but little is known about their impact on inpatient outcomes. Aims: To better understand the role of dyskalaemia in hospital in-patients, we assessed the epidemiology of potassium disorders among CKD patients, and the association between admission potassium and inpatient mortality or intensive care unit (ICU) requirement. Methods: This retrospective hospital-based cohort study (n = 11 156) included patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 admitted to Austin Health between 2014 and 2018 and who had an admission potassium value. Dialysis patients or those with a renal transplant were excluded. Multivariate logistic analysis was conducted to identify factors associated with hyperkalaemia (=5.5 mmol/L) and hypokalaemia (<3.5 mmol/L). Odds ratios for inpatient mortality and ICU admission between potassium categories were obtained by multivariate regression with adjustments for demographics, renal function and comorbidities. Results: Hyperkalaemia and hypokalaemia were present in 6.86% and 2.94% of hospital admissions respectively. In multivariate regression male sex, lower eGFR, diabetes and cardiac failure were associated with higher odds of hyperkalaemia. Thiazide diuretics, loop diuretics, infectious disease and endocrine pathology were associated with higher odds of hypokalaemia. A U-shaped association was noted between potassium and inpatient mortality. Potassium <4.0 mmol/L and =5.0 mmol/L was associated with increased mortality. Only patients with potassium =5.5 mmol/L had increased ICU admission risk. Conclusion: Derangements in potassium frequently occur in CKD inpatients and are independently associated with higher mortality and ICU requirement. Further studies are required to determine whether interventions to maintain normokalaemia improve outcomes in this population. [ABSTRACT FROM AUTHOR]

Background: Driving is a complex task requiring multiple cognitive domains and the musculoskeletal system. Cognitive dysfunction is associated with driving impairment. Dialysis patients are known to have a high prevalence of cognitive impairment and other comorbidities, and may be at risk of driving impairment. No Australian guidelines address driving safety in dialysis patients. Aims: To estimate the proportion of dialysis patients who were driving and those at risk of driving impairment, and to investigate the agreement between objective and subjective markers of risk. Methods: This single‐centre study involved dialysis patients voluntarily completing two questionnaires relating to risk of driving impairment; the first questionnaire focussed on objective markers, and the second questionnaire focussed on subjective markers. Risk of driving impairment was established using pre‐determined criteria, and the agreement between objective and subjective markers was estimated using Cohen kappa. Results: A total of 44.8% (99/221) of patients participated; 76.8% (76/99) of participants were driving, and 76.3% (58/76) of drivers were at risk of driving impairment. Factors associated with at‐risk driving included post dialysis dizziness, leg weakness or numbness, falling asleep while driving and hypoglycaemia. Sixteen patients reported collisions since commencing dialysis. The questionnaires displayed slight agreement (Cohen kappa = 0.20) between objective and subjective markers. Conclusions: Dialysis patients are at risk of driving impairment based on self‐reported questionnaire responses. Discrepancies between patients' perceptions and objective markers were apparent. Further research into appropriate risk assessments, as well as development of guidelines to aid in determining driving safety in dialysis patients, is needed. [ABSTRACT FROM AUTHOR]

Understanding the factors driving population structure in marine mammals is needed to evaluate the impacts of previous exploitation, current anthropogenic threats, conservation status, and success of population recovery efforts.Sperm whales are characterized by a worldwide distribution, low genetic diversity, complex patterns of social and genetic structure that differ significantly within and between ocean basins, and a long history of being commercially whaled. In Australia, sperm whales from the (International Whaling Commission assigned) southern hemisphere 'Division 5' stock were very heavily exploited by whaling.The present study assessed the potential effects of whaling on the genetic diversity of sperm whales in Australia and the population genetic structure of these whales within a global context. A combination of historical and contemporary sperm whale samples (n = 157) were analysed across six regions, from south‐eastern Australia ('Division 6' stock in the Pacific Ocean) to south‐western Australia ('Division 5' stock in the Indian Ocean).Sperm whales sampled from the 'Division 5' and 'Division 6' stocks belong to the same population based on nuclear and mitochondrial DNA (mtDNA) analyses. Four novel sperm whale mtDNA haplotypes were identified in animals from Australian waters. Levels of genetic diversity were low in Australian sperm whales but were similar to those previously reported for populations in the Indian and Pacific Oceans.Given the genetic distinctiveness of sperm whales in Australian waters from other regions in the Pacific and Indian Oceans, and the lack of recovery in population numbers, further scientific studies are needed to increase our understanding of population dynamics and the effectiveness of threat management strategies in this species. [ABSTRACT FROM AUTHOR]

Summary: Activation of the heterotrimeric energy‐sensing kinase AMP‐activated protein kinase (AMPK) has been reported to improve experimental diabetic kidney disease. We examined the effect of type 1 diabetes in wild‐type (WT) mice and mice lacking the β1 subunit of AMPK (AMPK β1−/− mice), which have reduced AMPK activity in kidneys and other organs. Diabetes was induced using streptozotocin (STZ) and the animals followed up for 4 weeks. Hyperglycaemia was more severe in diabetic AMPK β1−/− mice, despite the absence of any difference in serum levels of insulin, adiponectin and leptin. There was no change in AMPK activity in the kidneys of diabetic WT mice by AMPK activity assay, or phosphorylation of either the αT172 activation site on the α catalytic subunit of AMPK or the AMPK‐specific phosphosite S79 on acetyl CoA carboxylase 1 (ACC1). Phosphorylation of the inhibitory αS485 site on the α subunit of AMPK was significantly increased in the WT diabetic mice compared to non‐diabetic controls. Despite increased plasma glucose levels in the diabetic AMPK β1−/− mice, there were fewer myofibroblasts in the kidneys compared to diabetic WT mice, as evidenced by reduced α‐smooth muscle actin (α‐SMA) protein by Western blot, mRNA by qRT‐PCR and fewer α‐SMA‐positive cells by immunohistochemical staining. Albuminuria was also reduced in the AMPK β1−/− mice. In contrast to previous studies, therefore, myofibroblasts were reduced in the kidneys of AMPK β1−/− diabetic mice compared to diabetic WT mice, despite increased circulating glucose, suggesting that AMPK can worsen renal fibrosis in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to examine the efficacy of advance care planning (ACP) to improve the likelihood that end‐stage kidney disease (ESKD) patient's preferences will be known and adhered to at end‐of‐life. Methods: A case‐control study of a nurse‐led ACP programme in adults with ESKD from a major tertiary hospital. The primary outcome was the proportion of patients whose preferences were known (by substitute decision maker and/or clinicians) and adhered to by their treating doctors. Secondary measures were health system resource use and costs ($AUD) for a nurse‐led ACP intervention in the last 12‐months of life. Results: In total, 57 cases (38 men, mean age 73.8 years) and 57 historical controls (38 men, mean age 74.0 years) were included. Cases (38/57, 67%) were significantly more likely than controls (15/57, 26%) to have their preferences known and adhered to by their treating doctor at end‐of‐life (P < 0.001). Cases (33/40, 83%) were also significantly more likely to withdraw from dialysis in accordance with their preferences than controls (11/33, 33%) (P < 0.001). For cases, the average hospital costs in the last 12 months of life was AUD $99 077 (SD = $71 002) per patient. The total cost of the ACP programme in 2010/2011 was AUD $26 821. Conclusion: Advance care planning was associated with improvements in end‐of‐life care preferences being known and adhered to for people with ESKD. Summary at a Glance: Advance care planning (ACP) aims to empower patients, with the support of their caregivers, to consider their current and future treatment goals in the context of their own preferences and values. This study showed that ACP was associated with improvements in end‐of‐life care preferences being known and adhered to In addition, the average cost of providing ACP per‐patient was equal to 0.5% of the average hospital costs per‐patient in the last 12‐months of life. [ABSTRACT FROM AUTHOR]

This paper uses a present value approach to show that price movements for equity indices in a sample of European stock markets can be traced to legal origin, institutional, and corporate financial factors. The present value literature states that stock indices move due to changes either in discount rates, dividend growth, or a combination of the two. Empirically, little is known about the mechanism through which legal, institutional, and corporate financial factors influence these variables, especially in a European context. The current paper attempts to plug this gap in the literature. Using the state space approach, we show that although expected returns are highly persistent, expected dividend growth tends to vary across the sample. Movements in markets are mainly due to changes in the discount rate. However, there appears to be a difference in the proportion of movements attributable to discount rate and dividend growth components. Stock markets in civil law countries tend to have a stronger link with the dividend growth variables as well as market size and activity measures. Expected dividend growth is also driven by profitability factors in both types of country. By contrast, there is no strong evidence of corporate indicators influencing expected returns. [ABSTRACT FROM AUTHOR]

Abstract: The overall aim in the development of the Local Ecological Footprinting Tool (LEFT) was to design a web‐based tool that could provide quickly obtained quantitative data on ecological risk to assist landowners when making land‐use change decisions. The Local Ecological Footprinting Tool works for almost any region in the world and uses freely available satellite imagery, biotic and abiotic data from existing global databases, models and algorithms to deliver a customised report for a selected area within one hour of job submission. Biotic data automatically obtained for a selected landscape includes terrestrial vertebrate and plant species occurrence data, information on their conservation status and remotely sensed vegetation productivity. Abiotic information obtained includes temperature, precipitation, water availability, insolation, topography, elevation, distribution of urban infrastructure and location of wetlands. The tool performs a number of analyses on the biotic and abiotic data to produce maps for the selected area at a 30 m resolution depicting land cover type, numbers of globally threatened terrestrial vertebrate and plant species, beta‐diversity of terrestrial vertebrates and plants, habitat intactness, wetland habitat connectivity, numbers of migratory species and vegetation resilience. Results are also aggregated to produce a summary map demonstrating areas of high and low ecological risk across the selected area. The Local Ecological Footprinting Tool has been designed to be intuitive to use, requiring no specialised software or user expertise. Input is extremely easy and requires the user to highlight the area of interest on a map or using grid co‐ordinates. Output is delivered via the web application and comprises a customised PDF containing the maps and a zip file of geographical information system (GIS) data for the area requested. Users may run an unlimited number of LEFT analyses and download reports free of charge. In addition to the free tool described in this paper, there is also a paid service: individual LEFT analyses can be upgraded for a charge to allow access to the geographically subsetted datasets generated for each report. These data are supplied as a zip file containing raster datasets for the layers in the LEFT analysis in GeoTIFF format. These can be opened and queried in a GIS software package. [ABSTRACT FROM AUTHOR]

The high-energy requirement of the kidney and the importance of energy metabolism in renal physiology has been appreciated for decades, but only recently has there emerged a strong link between impaired renal energy metabolism and chronic kidney disease ( CKD). The mechanisms underlying the association between changes in energy metabolism and progression of CKD, however, remain poorly understood. A new study from Qiu and colleagues reported in the Journal of Pathology has advanced this understanding by showing that, after renal injury, the energy sensor AMPK inhibits epithelial-mesenchymal transition and inflammation, processes important in the pathogenesis of CKD. Furthermore, this study identifies an interaction between AMPK and CK2β as an important mechanism in the anti-fibrotic effect. CK2β has previously been shown to interact with STK11 (also known as LKB1) to regulate cellular polarity. These findings are consistent with the known roles of the LKB1-AMPK pathway in sustaining cellular energy homeostasis and epithelial cell polarity, and add to growing evidence linking the suppression of energy metabolism to CKD. They emphasize the importance of energy metabolism in general and the LKB1-AMPK axis in particular as key investigational and therapeutic targets in the battle against CKD. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim In the Australian state of Victoria, the Renal Health Clinical Network ( RHCN) of the Department of Health Victoria established a Renal Key Performance Indicator ( KPI) Working Group in 2011. The group developed four KPIs related to chronic kidney disease and dialysis. A transplant working group of the RHCN developed two additional KPIs. The aim was to develop clinical indicators to measure performance of renal services to drive service improvement. Methods A data collection and benchmarking programme was established, with data provided monthly to the Department using a purpose-designed website portal. The KPI Working Group is responsible for analysing data each quarter and ensuring indicators remain accurate and relevant. Each indicator has clear definitions and targets, and assess (i) patient education, (ii) timely creation of vascular access for haemodialysis, (iii) proportion of patients dialysing at home, (iv) incidence of dialysis-related peritonitis, (v) incidence of pre-emptive renal transplantation, and (vi) timely listing of patients for deceased donor transplantation. Results Most KPIs have demonstrated improved performance over time with limited gains notably in two: the proportion of patients dialysing at home ( KPI 3) and timely listing patients for transplantation ( KPI 6). Conclusion KPI implementation has been established in Victoria for 2 years, providing performance data without additional funding. The six Victorian KPIs are measurable, relevant and modifiable, and implementation relies on enthusiasm and goodwill of physicians and nurses involved in collecting data. The KPIs require further evaluation, but adoption of a similar programme by other jurisdictions could lead to improved national outcomes. [ABSTRACT FROM AUTHOR]

In humans, mutations of the Intrinsic lysosomal protein SCARB2 are associated with myoclonic epilepsy, collapsing focal and segmental glomerulosclerosis, and tubular proteinuria. Mice with deficiency of Limp-2 (the murine homologue) develop tubular proteinuria but not focal and segmental glomerulosclerosis and they have a defect in macrophage function. To further elucidate the role of Limp-2 in immune function, we induced anti-glomerular basement membrane (GBM) model of crescentic glomerulonephritis in wild-type (WT) and Limp-2-l- littermates by intraperitoneal injections of nephrotoxic sheep serum. Renal injury and immune responses were assessed on day 14. Compared with WT, Limp-2-l- mice had significantly reduced crescent formation, interstitial inflammation and a trend to reduced tubulointerstitial injury. On day 1 during the heterologous phase of the disease, albuminuria was significantly increased in WT but not in Limp-2 -l- mice. On day 14, albuminuria and renal function were similar in the two groups. There was, however, a significant reduction in the influx of glomerular macrophages and CD4+ T cells in Limp-2 -l- mice. Interleukin (IL)-4 and macrophage chemoattractant protein-1 (MCP-l) mRNA expression levels were significantly reduced. Despite the reduction in numbers of infiltrating cells, flow cytometry showed no difference in macrophage or T-cell numbers in the peripheral blood from untreated mice. The systemic humoral immune response, determined by glomerular mouse immunoglobulin G (IgG) deposition and mouse anti-sheep IgG subclass production, was similar in both groups. These data suggest that absence of Limp-2 reduces inflammation in experimental crescentic glomerulonephritis with decreased macrophage and T-cell infiltration in the kidney. It suggests an important role for Limp-2 in mediating the inflammatory response. [ABSTRACT FROM AUTHOR]

This study provides empirical evidence in relation to a growing body of literature concerned with the 'socialisation' effects of accounting and business education. A prevalent criticism within this literature is that accounting and business education in the United Kingdom and the United States, by assuming a 'value-neutral' appearance, ignores the implicit ethical and moral assumptions by which it is underpinned. In particular, it has been noted that accounting and business education tends to prioritise the interests of shareholders above all other stakeholder groups. This paper reports on the results of a set of focus group interviews with both undergraduate accounting students and students commencing their training with a professional accounting body. The research explores their perceptions about the purpose of accounting and the objectives of business. The findings suggest that both university and professional students' views on these issues tend to be informed by an Anglo-American shareholder discourse, whereby the needs of shareholders are prioritised. Moreover, this shareholder orientation appeared to be more pronounced for professional accounting students. [ABSTRACT FROM AUTHOR]

CONTEXT Burnout is prevalent amongmedical students and is a predictor of subsequent serious consideration of dropping out of medical school and suicide ideation. Understanding of the factors that protect against burnout is needed to guide student wellness programmes. METHODS A total of 1321 medical students attending five institutions were studied longitudinally (2006-2007). The surveys included standardised instruments to evaluate burnout, quality of life, fatigue and stress. Additional items explored social support, learning climate, life events, employment status and demographics. Students who did not have burnout at either time-point (resilient students) were compared with those who indicated burnout at one or both time-points (vulnerable students) using a Wilcoxon-Mann-Whitney test or Fisher's exact test. Similarly, the differences between those who recovered and those who were chronically burned out were also compared in students with burnout at the first time-point. Logistic regression modelling was employed to evaluate associations between the independent variables and resiliency to and recovery from burnout. RESULTS Overall, 792 (60.0%) students completed the burnout inventory at both timepoints. No differences in demographic characteristics were observed between resilient (290 /792 [36.6%]) and vulnerable (502 / 792 [63.4%]) students. Resilient students were less likely to experience depression, had a higher quality of life, were less likely to be employed, had experienced fewer stressful life events, reported higher levels of social support, perceived their learning climate more positively and experienced less stress and fatigue (all p < 0.05) than vulnerable students. On multivariable analysis, perceiving student education as a priority for faculty staff, experiencing less stress, not being employed and being a minority were factors independently associated with recovery from burnout. CONCLUSIONS Modifiable individual factors and learning climate characteristics including employment status, stress level and perceptions of the prioritising of student education by faculty members relate to medical students' vulnerability to burnout. [ABSTRACT FROM AUTHOR]

Activation of nuclear factor-kappa B (NF-κB) is one of the most important pro-inflammatory mechanisms in disease. In this study, we show that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), an intermediate in nucleoside metabolism, inhibits signalling by NF-κB in three cell types, including bovine aortic endothelial cells (BAEC). The block in the NF-κB signalling pathway occurred beyond degradation of IκB-α and movement of p65 into the nucleus of BAEC. There was, however, reduced binding of NF-κB from AICAR-treated cells to a κB-consensus oligonucleotide, suggesting that part of the mechanism was a reduction in NF-κB DNA-binding activity. Although AICAR is metabolized to ZMP and then adenosine, adenosine had no effect on activation of an NF-κB reporter. ZMP, however, activates the metabolic stress-sensing AMP-activated protein kinase (AMPK). Transfection of active AMPK into BAEC reduced NF-κB reporter activity compared with a kinase-dead mutant, suggesting that part of the ability of AICAR to inhibit NF-κB signalling is due to activation of AMPK. Inhibition of NF-κB signalling may be important in the anti-inflammatory action of drugs such as sulfasalazine and methotrexate, which led to the accumulation of AICAR within target cells. [ABSTRACT FROM AUTHOR]

The decline in renal and cardiac function with advancing age predisposes older people to abnormalities in renal function and electrolyte disturbances. The widespread availability of the estimated glomerular filtration rate has highlighted the high incidence of chronic kidney disease in the elderly, which is supported by data demonstrating that the elderly are the largest cohort undergoing kidney dialysis in the general population. Older people are also susceptible to electrolyte disturbances, especially if they have concomitant diseases, such as heart failure, and are receiving diuretics and blockers of the reninangiotensin system. Management of these patients requires skill, as well as realistic objectives. In this article we discuss some of the issues pertaining to renal and electrolyte abnormalities experienced by older people. [ABSTRACT FROM AUTHOR]

Objectives Little is known about specific personal and professional factors influencing student distress. The authors conducted a comprehensive assessment of how learning environment, clinical rotation factors, workload, demographics and personal life events relate to student burnout. Methods All medical students ( n = 3080) at five medical schools were surveyed in the spring of 2006 using a validated instrument to assess burnout. Students were also asked about the aforementioned factors. Results A total of 1701 medical students (response rate 55%) completed the survey. Learning climate factors were associated with student burnout on univariate analysis (odds ratio [OR] 1.36–2.07; all P ≤ 0.02). Being on a hospital ward rotation or a rotation requiring overnight call was also associated with burnout (ORs 1.69 and 1.48, respectively; both P ≤ 0.02). Other workload characteristics (e.g. number of admissions) had no relation to student burnout. Students who experienced a positive personal life event had a lower frequency of burnout (OR 0.70; P ≤ 0.02), whereas those who experienced negative personal life events did not have a higher frequency of burnout than students who did not experience a negative personal life event. On multivariate analysis personal characteristics, learning environment and personal life events were all independently related to student burnout. Conclusions Although a complex array of personal and professional factors influence student well-being, student satisfaction with specific characteristics of the learning environment appears to be a critical factor. Studies determining how to create a learning environment that cultivates student well-being are needed. [ABSTRACT FROM AUTHOR]

This article presents findings from a study of African immigration to Ireland. Set against a background description of who these recent immigrants are and why they come, this research, based primarily in a Dublin maternity hospital, looks at the experiences of pregnant and post-partal African women to explore questions surrounding use of maternity services and their relationship to larger issues of integration into Irish society. This gendered segment of the population is of particular interest, as the phenomenon of Irish-born children to non-national parents has been a lightning rod issue in immigration debates in Ireland, leading to a June 2004 referendum limiting access to citizenship by birth in unprecedented ways. Ireland, long a country characterized by emigration, only recently transitioned to a nation of net immigration, and, as such, is grappling with the implications of its rapidly changing ethnic make-up in questions of race and racism, allocation of social welfare entitlements, and effective health and human services delivery. Through this exploration of the phenomenon of inscribing immigration debates on African women’s bodies, this article highlights racism, family reunification, the right to work, and the lengthy process of adjudicating immigration claims as significant obstacles to integration into Irish society. Through this analysis, this article also provides empirical data that feed into ongoing debates about the meaning of “African diaspora.” [ABSTRACT FROM AUTHOR]

The age-dependent changes in the kidney are often debilitating, can be life-threatening and are a significant cause of increasing health costs worldwide. Excessive fibrosis, a general lack of regenerative ability and an increase in apoptosis in cells that determine healthy renal function work together to cause chronic kidney disease. This review provides information on the molecules and mechanisms that determine the age-dependent effects in the kidney, and in particular, the effects of cellular metabolism and oxidant handling on the ageing kidney. With a better understanding of the influence of ageing on the structural and functional alterations that occur, new targeted therapies may be developed to minimize renal damage and promote health in the elderly. [ABSTRACT FROM AUTHOR]

This paper examines the financial performance of the FTSE4Good indices; the indices include companies from different geographical areas on the basis of pre-determined social responsibility criteria: currently environmental sustainability, relationships with stakeholders, attitudes to human rights, supply chain labour standards and the countering of bribery. The results indicate that over the period of analysis from 1996 to 2005 these indices outperformed their relevant benchmarks. However, most of this outperformance was due to risk differences between the FTSE4Good indices and their benchmarks. In addition, much of the outperformance arose in the period before the indices could be used by practitioners. Nevertheless, the results suggest that investors who invest in a portfolio of companies that satisfy FTSE4Good's corporate social responsibility criteria do no worse than their counterparts who do not follow a socially responsible strategy when purchasing equities. Copyright © 2007 John Wiley & Sons, Ltd and ERP Environment. [ABSTRACT FROM AUTHOR]

AMP-activated protein kinase (AMPK) is a key energy sensor, known to regulate energy metabolism in diverse cell types. Hypoxia is encountered frequently in the microenvironments of inflammatory lesions and is a critical regulator of function in inflammatory cells. Energy deficiency is one of the consequences of hypoxia, but its potential role in modulating leucocyte function has received little attention. Using micropore chemotaxis assays to assess migratory responses of the monocyte-like cell line U937, it was found that the AMPK activators AICAR and phenformin rapidly reduced random migration (chemokinesis) as well as chemotaxis due to stromal cell-derived factor (SDF)1α. There was an approximate 50% reduction in both chemokinesis and chemotaxis following 30 min preincubation with both AICAR and phenformin ( P < 0.01), and this continued with up to 24 h preincubation. The binding of SDF1α to its receptor CXCR4 was unaltered, suggesting AMPK was acting on downstream intracellular signalling pathways important in cell migration. As AMPK and statins are known to inhibit HMG CoA reductase, and both reduce cell migration, the effect of mevastatin on U937 cells was compared with AMPK activators. Mevastatin inhibited cell migration but required 24 h preincubation. As expected, the inhibitory effect of mevastatin was associated with altered subcellular localization of the Rho GTPases, RhoA and cdc42, indicating decreased prenylation of these molecules. Although the effect of AMPK activation was partially reversed by mevalonate, this was not associated with altered subcellular localization of Rho GTPases. The data suggest that activation of AMPK has a general effect on cell movement in U937 cells, and this is not due to inhibition of HMG CoA reductase. These are the first data to show an effect of AMPK on cell movement, and suggest a fundamental role for energy deficiency in regulating cellular behaviour. [ABSTRACT FROM AUTHOR]

The glomerular filtration barrier of the kidney can no longer be considered as an inert and adynamic structure, viewed by electron microscopy. Molecular biology, medical genetics and protein chemistry have enabled us to further understand the complex structure and function of this highly specialized barrier of the kidney. Minor aberrations of physiology can lead to fatal disease. Recent advances in the understanding of the physiology of endothelial cells, glomerular epithelial cells and the glomerular basement membrane and its components, and how these relate to disease, will be considered systematically. [ABSTRACT FROM AUTHOR]

Theβ-d-endoglycosidase, heparanase, is emerging as an important contributor to the pathogenesis of proteinuria. The purpose of the present study therefore was to examine the role of heparanase in a model of accelerated anti-glomerular basement disease (anti-GBM).Accelerated anti-GBM disease was induced and animals sacrificed at day 10 to establish heparanase expression using immunohistochemistry and western blot analysis. In addition, cortex was isolated from normal and diseased glomeruli to determine if mRNA levels altered with disease. A previously validated anti-heparanase antibody associated with proteinuria reduction, in a model of membranous nephropathy, was administered prior to disease induction to establish its impact on protein excretion in this model.At day 10 of anti-GBM disease, an increase in glomerular heparanase was shown using immunohistochemistry. Sequential staining studies revealed that this increase was associated with glomerular endothelial, epithelial cells and invading ED-1-positive inflammatory cells. RT-PCR revealed an insignificant 1.2-fold induction of mRNA at day 10 of disease. Western blot analysis of kidney cortex confirmed that the active 58-kDa heparanase species was restricted to diseased kidney at day 10. The inactive 65-kDa precursor, however, was found only in cortex derived from normal kidney. Proteinuria at day 10 of disease was significantly reduced, in the absence of altered rat anti-sheep antibody titres, after administration of a validated polyclonal anti-heparanase antibody (P < 0.05). Furthermore, sheep IgG deposition was not altered by administration of the anti-heparanase antibody.These data suggest that heparanase contributes to the pathogenesis of proteinuria in a model of anti-GBM disease. [ABSTRACT FROM AUTHOR]

Corporate governance as a coherent notion and independent topic of academic and practitioner interest has developed rapidly in the last ten years. In particular, most countries have seen the publication of vast numbers of regulatory reports outlining best practice in handling the issues that arise from the increased prominence of the governance concept. Although a vast literature exists on the implications of an Initial Public Offering (IPO) for financial performance and ownership structure, few investigations have communicated directly with issuing firms and analysed the practical difficulties encountered on a day-to-day basis when a company decides to float. In particular, very few studies have sought to examine what corporate governance changes, if any, are made in the process. This note reports the findings of a questionnaire survey and a series of interviews with practitioners about the changes that are made before and after a sample of IPOs in the UK. [ABSTRACT FROM AUTHOR]

This paper reports on a questionnaire survey sent to environmental managers in quoted UK firms from environmentally sensitive sectors. A total of 58 usable responses was received, with most but not all being returned by environmental managers. While contextual information regarding perceptions of their companies' environmental sensitivity and management systems was sought, the main focus of the questionnaire was on respondents' views about stakeholder concerns. There was broad agreement that external stakeholders attached importance to environmental communications. The results indicate that respondents' perceptions of these issues were associated with the formality of their internal management systems and with the role of the respondents within their firms. It was also found that shareholders were thought to be the least interested stakeholder group. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment. [ABSTRACT FROM AUTHOR]

SUMMARY: In the kidney, heparin-binding epidermal growth factor-like growth factor (HB-EGF) and its receptors, epidermal growth factor–receptor (EGF-R) and human epidermal receptor 4 (erbB4/ HER4), may be important in the response of cells to tissue injury. To further define the role of HB-EGF, we have determined its distribution in the accelerated anti-GBM model of kidney disease. Within the glomerulus, immunohistochemical staining showed increased HB-EGF expression in podocytes and infiltrating macrophages. This was associated with strong de novo expression of erbB4/HER4 on podocytes. These data suggest that increased expression of HB-EGF and erbB4/HER4 is a response to inflammation in the glomerulus in accelerated anti-GBM disease. To determine the potential role of HB-EGF in anti-GBM disease, a blocking monoclonal antibody against HB-EGF (DE10) was administered by intravenous injection. There was, however, no significant difference in the extent of 24 h urinary protein, renal function, or histological appearances. The effects of blocking HB-EGF, therefore, may be masked by the redundancy in the EGF growth factor family. [ABSTRACT FROM AUTHOR]

This study revisits the dividend–signalling hypothesis by examining the post–announcement performance of U.K. companies which disclose dividend and earnings news to the capital market on the same day. For this purpose, we first analyse market–adjusted excess returns for three periods around the announcement and then examine the financial performance in the year of the announcement and in the subsequent five–year period. The near announcement excess returns and the announcement–year financial profiles provide strong evidence in support of the dividend–signalling hypothesis. However, in contrast to the predictions of the hypothesis, the longer–term results suggest that the companies which announce a reduction in both dividends and earnings (bad news companies) outperform their dividend–increasing counterparts. [ABSTRACT FROM AUTHOR]

This paper is concerned with the attempts to explain the disclosure of social and environmental information in the annual reports of large companies by reference to observable characteristics of those companies. An extensive literature has sought to establish whether variables such as corporate size, profit and industry segments can explain corporations' disclosure practices. The results from that predominantly North American and Australasian literature are largely inconclusive. This paper provides an extension of that literature by considering a more disaggregated specification of social and environmental disclosure and by employing a detailed time-series data set. By so doing, the paper tests two possible explanations for the inconclusiveness of prior research: namely that any relationships between corporate characteristics and disclosure are dependent upon the type of disclosure and that any such relationships are not stable through time. The results provide support for these explanations as sufficient, if not necessary, conditions for explaining the inconsistency in prior results. [ABSTRACT FROM AUTHOR]

SUMMARY:It is becoming increasingly evident that the transcription factor, nuclear factor-kappa B (NF-κB) is at the heart of the inflammatory response in all tissues, including the kidney. Studies in both human glomerulonephritis and experimental disease models provide either direct or circumstantial evidence for the activation of NF-κB. Moreover, it now appears that many existing anti-inflammatory or immunosuppressive drugs appear to exert at least part of their action through the inhibition of NF-κB. However, the widely used inhibitors of NF-κB (especially steroids and cyclosporin) are not completely effective in the treatment of glomerulonephritis. These observations raise two critical questions; first, whether there are cell-specific differences in the action of NF-κB inhibitors and, second, whether it is more important to inhibit NF-κB in glomerular cells or in cells of the immune system. At present, there is insufficient evidence to answer these questions as most work in this area has concentrated on NF-κB in lymphocytes. Activation of NF-κB in the cells of the kidney, however, suggests that they may actively contribute to inflammation. Whether agents known to inhibit NF-κB in the immune system, such as steroids and cyclosporin, also inhibit NF-κB in glomerular cells is not well established. Drugs able to effectively inhibit NF-κB in tissues therefore could provide a new approach to the treatment of glomerulonephritis. It is possible that suitable agents already exist among the significant number of drugs reported to inhibit NF-κB. If not, the recent identification of kinases that activate NF-κB will lead to the development of agents to inhibit this central, proinflammatory pathway. It will be of great interest to determine whether they offer anything over corticosteroids and cyclosporin, the more ‘traditional’ inhibitors of NF-κB in glomerulonephritis. [ABSTRACT FROM AUTHOR]

This article examines the British stock market reaction to the announcement of different types of capital expenditures. The findings suggest that investors' response to this news depends on whether the project is undertaken by an individual firm or as part of a joint venture and whether the investment generates cash immediately or recoups its investment only after a period of several years. As a rule, only announcements of joint ventures were associated with a positive market reaction; no significant abnormal returns followed single-company expenditure news. These British results for projects announced by individual firms therefore appear to be consistent with the second scenario outlined in the introduction, in which the market is unsurprised when news of capital expenditure projects are issued by large, publicly-traded companies. Joint ventures, on the other hand, do appear to surprise the market and enhance market expectations about the future prospects of the participating firms. Amongst the investment announcements made by individual firms, the abnormal returns which followed the disclosure of immediate cash-generating projects were found to be positively related to the magnitude of the proposed expenditure.

The article presents a study which examines the links between ownership structure, firm performance and CEO turnover for a sample of firms over the period 1989-1992 in Great Britain. The authors find evidence of managerial entrenchment which means that managers with high equity stakes are less likely to be removed from office when firm performance is poor, whereas managers with low ownership stakes are under greater threat of dismissal if they under-perform. They also document evidence of shareholder wealth effects associated with CEO turnover. Perhaps the most important issued identified by the paper is apparently very low level of stock ownership at which managers seem to become entrenched and partially protected against the threat of dismissal.

The article cites a study that proposes to correct deficiencies, utilizing quantitative procedures to delineate homogeneous subgroups of pain patients with un-elevated Minnesota Multiphasic Personality Inventories. Researchers state that subsequent actuarial analyses that provide base rate data for respective subgroups across a broad range of pain-related measures facilitate the accurate appraisal of psychological factors within this population. Results of the study revealed that interpretive approaches to un-elevated pain profiles have been varied.

Presents a study which examined the question of persistence in stock market returns. Methodology used in the tests of persistence; Data and results; Analysis of whether the winner-loser effect exists for weekly returns of a sample of shares traded on the London Stock Exchange; Conclusions.

Presents the abstract 'No Pain--No Haematuria Syndrome,' by Kathleen Kan, Matthew Roberts, Margaret B. Fraenkel and Frank L. Ierino.

Objective: The major human Fc receptor, FcgammaRIIa, is the most widespread activating FcR. Our aim was to determine the role of FcgammaRIIa in a transgenic mouse model of immune complex-mediated autoimmunity and to characterize the development of spontaneous autoimmune disease., Methods: Arthritis was induced in normal and FcgammaRIIa-transgenic mice by immunization with type II collagen (CII) or by transfer of arthritogenic anti-CII antibodies. Also, mice that spontaneously developed autoimmune disease were assessed by clinical scoring of affected limbs, histology and serology, and measurement of autoantibody titers and cytokine production., Results: FcgammaRIIa-transgenic mice developed collagen-induced arthritis (CIA) more rapidly than did archetypal CIA-sensitive DBA/1 (H-2q) mice, while nontransgenic C57BL/6 (H-2b) mice did not develop CIA when similarly immunized. Passive transfer of a single dose of anti-CII antibody induced a more rapid, severe arthritis in FcgammaRIIa-transgenic mice than in nontransgenic animals. In addition, most immune complex-induced production of tumor necrosis factor alpha by activated macrophages occurred via FcgammaRIIa, not the endogenous mouse FcR. A spontaneous, multisystem autoimmune disease developed in aging (>20 weeks) transgenic mice (n = 25), with a 32% incidence of arthritis, and by 45 weeks, all mice had developed glomerulonephritis and pneumonitis, and most had antihistone antibodies. Elevated IgG2a levels were seen in mice with CIA and in those with spontaneous disease., Conclusion: The presence of enhanced passive and induced autoimmunity, as well as the emergence of spontaneous autoimmune disease at 20-45 weeks of age, suggest that FcgammaRIIa is a very important factor in the pathogenesis of autoimmune inflammation and a possible target for therapeutic intervention.