Using staged teaching and assessment approaches to facilitate inter-university collaboration and problem-based learning

This article describes the segmented module design and problem-based learning approaches employed to enable parts of a higher education environmental health module (course) to be shared between universities in Wales, Northern Ireland, and Australia. The module requires students to identify the needs and assets of a community then design community-based interventions to address problems and undertake an evaluation of those interventions.Accreditation body and the degree program learning outcome requirements in the UK and Australia were found to hold many comparable knowledge, skills, and graduate attribute criteria, eliminating a potential barrier for international learning and teaching collaboration between higher education institutions. Instead, barriers to collaboration were associated with institutional issues and practicalities such as timetabling and assessment requirements. Taking a segmented approach to module design allowed staged and varied levels of collaboration between participating institutions, all delivering modules (courses) with similar learning outcomes. This provided a more sustainable environment to facilitate shared learning and teaching and fostered closer relations between programs, within these constraining factors.Students using problem-based learning and its group-working component exhibited the development of leadership, communication, and independent learning skills

Systems and methods for short range RF communication

A method transmitting a message over at least one of a plurality of channels of a communications network is provided. The method comprises the steps of detecting a presence of jamming pulses in the at least one of the plurality of channels. The characteristics of the jamming pulses in the at least one of the plurality of channels is determined wherein the determined characteristics define at least interstices between the jamming pulses. The message is transmitted over the at least one of the plurality of channels wherein the message is transmitted within the interstices of the jamming pulse determined from the step of determining characteristics of the jamming pulses

Fibroblast growth factor receptor 3 activation plays a causative role in urothelial cancer pathogenesis in cooperation with Pten loss in mice

Although somatic mutations and overexpression of the tyrosine kinase fibroblast growth factor receptor 3 (FGFR3) are strongly associated with bladder cancer, evidence for their functional involvement in the pathogenesis remains elusive. Previously we showed that activation of Fgfr3 alone is not sufficient to initiate urothelial tumourigenesis in mice. Here we hypothesize that cooperating mutations are required for Fgfr3-dependent tumourigenesis in the urothelium and analyse a mouse model in which an inhibitor of Pi3k–Akt signalling, Pten, is deleted in concert with Fgfr3 activation (UroIICreFgfr3+/K644EPtenflox/flox). Two main phenotypical characteristics were observed in the urothelium: increased urothelial thickness and abnormal cellular histopathology, including vacuolization, condensed cellular appearance, enlargement of cells and nuclei, and loss of polarity. These changes were not observed when either mutation was present individually. Expression patterns of known urothelial proteins indicated the abnormal cellular differentiation. Furthermore, quantitative analysis showed that Fgfr3 and Pten mutations cooperatively caused cellular enlargement, while Pten contributed to increased cell proliferation. Finally, FGFR3 overexpression was analysed along the level of phosphorylated mTOR in 66 T1 urothelial tumours in tissue microarray, which supported the occurrence of functional association of these two signalling pathways in urothelial pathogenesis. Taken together, this study provides evidence supporting a functional role of FGFR3 in the process of pathogenesis in urothelial neoplasms. Given the wide availability of inhibitors specific to FGF signalling pathways, our model may open the avenue for FGFR3-targeted translation in urothelial disease. Copyright © 2014 Pathological Society of Great Britain and Ireland

Glucocorticoids regulate AKR1D1 activity in human liver in vitro and in vivo

Steroid 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates endogenous glucocorticoids and catalyses an important step in bile acid synthesis. Endogenous and synthetic glucocorticoids are potent regulators of metabolic phenotype and play a crucial role in hepatic glucose metabolism. However, the potential of synthetic glucocorticoids to be metabolised by AKR1D1 as well as to regulate its expression and activity has not been investigated. The impact of glucocorticoids on AKR1D1 activity was assessed in human liver HepG2 and Huh7 cells; AKR1D1 expression was assessed by qPCR and Western blotting. Genetic manipulation of AKR1D1 expression was conducted in HepG2 and Huh7 cells and metabolic assessments were made using qPCR. Urinary steroid metabolite profiling in healthy volunteers was performed pre- and post-dexamethasone treatment, using gas chromatography-mass spectrometry. AKR1D1 metabolised endogenous cortisol, but cleared prednisolone and dexamethasone less efficiently. In vitro and in vivo, dexamethasone decreased AKR1D1 expression and activity, further limiting glucocorticoid clearance and augmenting action. Dexamethasone enhanced gluconeogenic and glycogen synthesis gene expression in liver cell models and these changes were mirrored by genetic knockdown of AKR1D1 expression. The effects of AKR1D1 knockdown were mediated through multiple nuclear hormone receptors, including the glucocorticoid, pregnane X and farnesoid X receptors. Glucocorticoids down-regulate AKR1D1 expression and activity and thereby reduce glucocorticoid clearance. In addition, AKR1D1 down-regulation alters the activation of multiple nuclear hormone receptors to drive changes in gluconeogenic and glycogen synthesis gene expression profiles, which may exacerbate the adverse impact of exogenous glucocorticoids

Glucocorticoids regulate AKR1D1 activity in human liver in vitro and in vivo

Steroid 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates endogenous glucocorticoids and catalyses an important step in bile acid synthesis. Endogenous and synthetic glucocorticoids are potent regulators of metabolic phenotype and play a crucial role in hepatic glucose metabolism. However, the potential of synthetic glucocorticoids to be metabolised by AKR1D1 as well as to regulate its expression and activity has not been investigated. The impact of glucocorticoids on AKR1D1 activity was assessed in human liver HepG2 and Huh7 cells; AKR1D1 expression was assessed by qPCR and Western blotting. Genetic manipulation of AKR1D1 expression was conducted in HepG2 and Huh7 cells and metabolic assessments were made using qPCR. Urinary steroid metabolite profiling in healthy volunteers was performed pre- and post-dexamethasone treatment, using gas chromatography-mass spectrometry. AKR1D1 metabolised endogenous cortisol, but cleared prednisolone and dexamethasone less efficiently. In vitro and in vivo, dexamethasone decreased AKR1D1 expression and activity, further limiting glucocorticoid clearance and augmenting action. Dexamethasone enhanced gluconeogenic and glycogen synthesis gene expression in liver cell models and these changes were mirrored by genetic knockdown of AKR1D1 expression. The effects of AKR1D1 knockdown were mediated through multiple nuclear hormone receptors, including the glucocorticoid, pregnane X and farnesoid X receptors. Glucocorticoids down-regulate AKR1D1 expression and activity and thereby reduce glucocorticoid clearance. In addition, AKR1D1 down-regulation alters the activation of multiple nuclear hormone receptors to drive changes in gluconeogenic and glycogen synthesis gene expression profiles, which may exacerbate the adverse impact of exogenous glucocorticoids

What is the most ecologically-meaningful metric of nitrogen deposition?

Nitrogen (N) deposition poses a severe risk to global terrestrial ecosystems, and managing this threat is an important focus for air pollution science and policy. To understand and manage the impacts of N deposition, we need metrics which accurately reflect N deposition pressure on the environment, and are responsive to changes in both N deposition and its impacts over time. In the UK, the metric typically used is a measure of total N deposition over 1–3 years, despite evidence that N accumulates in many ecosystems and impacts from low-level exposure can take considerable time to develop. Improvements in N deposition modelling now allow the development of metrics which incorporate the long-term history of pollution, as well as current exposure. Here we test the potential of alternative N deposition metrics to explain vegetation compositional variability in British semi-natural habitats. We assembled 36 individual datasets representing 48,332 occurrence records in 5479 quadrats from 1683 sites, and used redundancy analyses to test the explanatory power of 33 alternative N metrics based on national pollutant deposition models. We find convincing evidence for N deposition impacts across datasets and habitats, even when accounting for other large-scale drivers of vegetation change. Metrics that incorporate long-term N deposition trajectories consistently explain greater compositional variance than 1–3 year N deposition. There is considerable variability in results across habitats and between similar metrics, but overall we propose that a thirty-year moving window of cumulative deposition is optimal to represent impacts on plant communities for application in science, policy and management

Multivariable model to predict an ACTH stimulation test to diagnose adrenal insufficiency using previous test results

Context The adrenocorticotropin hormone stimulation test (AST) is used to diagnose adrenal insufficiency, and is often repeated in patients when monitoring recovery of the hypothalamo–pituitary–adrenal axis. Objective To develop and validate a prediction model that uses previous AST results with new baseline cortisol to predict the result of a new AST. Methods This was a retrospective, longitudinal cohort study in patients who had undergone at least 2 ASTs, using polynomial regression with backwards variable selection, at a Tertiary UK adult endocrinology center. Model was developed from 258 paired ASTs over 5 years in 175 adults (mean age 52.4 years, SD 16.4), then validated on data from 111 patients over 1 year (51.8, 17.5) from the same center, data collected after model development. Candidate prediction variables included previous test baseline adrenocorticotropin hormone (ACTH), previous test baseline and 30-minute cortisol, days between tests, and new baseline ACTH and cortisol used with calculated cortisol/ACTH ratios to assess 8 candidate predictors. The main outcome measure was a new test cortisol measured 30 minutes after Synacthen administration. Results Using 258 sequential ASTs from 175 patients for model development and 111 patient tests for model validation, previous baseline cortisol, previous 30-minute cortisol and new baseline cortisol were superior at predicting new 30-minute cortisol (R2 = 0.71 [0.49-0.93], area under the curve [AUC] = 0.97 [0.94-1.0]) than new baseline cortisol alone (R2 = 0.53 [0.22-0.84], AUC = 0.88 [0.81-0.95]). Conclusion Results of a previous AST can be objectively combined with new early-morning cortisol to predict the results of a new AST better than new early-morning cortisol alone. An online calculator is available at https://endocrinology.shinyapps.io/sheffield_sst_calculator/ for external validation

Education policy as an act of white supremacy: whiteness, critical race theory and education reform

The paper presents an empirical analysis of education policy in England that is informed by recent developments in US critical theory. In particular, I draw on ‘whiteness studies’ and the application of Critical Race Theory (CRT). These perspectives offer a new and radical way of conceptualising the role of racism in education. Although the US literature has paid little or no regard to issues outside North America, I argue that a similar understanding of racism (as a multifaceted, deeply embedded, often taken-for-granted aspect of power relations) lies at the heart of recent attempts to understand institutional racism in the UK. Having set out the conceptual terrain in the first half of the paper, I then apply this approach to recent changes in the English education system to reveal the central role accorded the defence (and extension) of race inequity. Finally, the paper touches on the question of racism and intentionality: although race inequity may not be a planned and deliberate goal of education policy neither is it accidental. The patterning of racial advantage and inequity is structured in domination and its continuation represents a form of tacit intentionality on the part of white powerholders and policy makers. It is in this sense that education policy is an act of white supremacy. Following others in the CRT tradition, therefore, the paper’s analysis concludes that the most dangerous form of ‘white supremacy’ is not the obvious and extreme fascistic posturing of small neonazi groups, but rather the taken-for-granted routine privileging of white interests that goes unremarked in the political mainstream

Genetic and Epigenetic Traits as Biomarkers in Colorectal Cancer

Colorectal cancer is a major health burden, and a leading cause of cancer-related deaths in industrialized countries. The steady improvements in surgery and chemotherapy have improved survival, but the ability to identify high- and low-risk patients is still somewhat poor. Molecular biology has, over the years, given insight into basic principles of colorectal cancer initiation and development. These findings include aberrations increasing risk of tumor development, genetic changes associated with the stepwise progression of the disease, and errors predicting response to a specific treatment. Potential biomarkers in colorectal cancer are extensively studied, and how the molecular aberrations relate to clinical features. Yet, little of this knowledge has been possible to transfer into clinical practice. In this review, an overview of colorectal cancer genetics will be given, as well as how aberrations found in this tumor type are proposed as biomarkers for risk prediction, as diagnostic tools, for prognosis or prediction of treatment outcome