Non-invasive techniques for imaging in-vivo human corneal sub basal nerve mapping and migration rate in diabetic neuropathy

Purpose Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic technique, which has been shown to diagnose and stratify the severity of diabetic neuropathy. Current morphometric techniques assess individual static images of the subbasal nerve plexus; this work explores the potential for non-invasive assessment of the wide-field morphology and dynamic changes of this plexus in vivo. Methods In this pilot study, laser scanning CCM was used to acquire maps (using a dynamic fixation target and semi-automated tiling software) of the central corneal sub-basal nerve plexus in 4 diabetic patients with and 6 without neuropathy and in 2 control subjects. Nerve migration was measured in an additional 7 diabetic patients with neuropathy, 4 without neuropathy and in 2 control subjects by repeating a modified version of the mapping procedure within 2-8 weeks, thus facilitating re-identification of distinctive nerve landmarks in the 2 montages. The rate of nerve movement was determined from these data and normalised to a weekly rate (µm/week), using customised software. Results Wide-field corneal nerve fibre length correlated significantly with the Neuropathy Disability Score (r = -0.58, p < 0.05), vibration perception (r = -0.66, p < 0.05) and peroneal conduction velocity (r = 0.67, p < 0.05). Central corneal nerve fibre length did not correlate with any of these measures of neuropathy (p > 0.05 for all). The rate of corneal nerve migration was 14.3 ± 1.1 µm/week in diabetic patients with neuropathy, 19.7 ± 13.3µm/week in diabetic patients without neuropathy, and 24.4 ± 9.8µm/week in control subjects; however, these differences were not significantly different (p = 0.543). Conclusions Our data demonstrate that it is possible to capture wide-field images of the corneal nerve plexus, and to quantify the rate of corneal nerve migration by repeating this procedure over a number of weeks. Further studies on larger sample sizes are required to determine the utility of this approach for the diagnosis and monitoring of diabetic neuropathy.

Elevated YKL40 is associated with advanced prostate cancer (PCa) and positively regulates invasion and migration of PCa cells

Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in tumours from patients with advanced stage cancers, including prostate cancer (PCa). The exact function of YKL40 is poorly understood, but it has been shown to play an important role in promoting tumour angiogenesis and metastasis. The therapeutic value and biological function of YKL40 are unknown in PCa. The objective of this study was to examine the expression and function of YKL40 in PCa. Gene expression analysis demonstrated that YKL40 was highly expressed in metastatic PCa cells when compared with less invasive and normal prostate epithelial cell lines. In addition, the expression was primarily limited to androgen receptor-positive cell lines. Evaluation of YKL40 tissue expression in PCa patients showed a progressive increase in patients with aggressive disease when compared with those with less aggressive cancers and normal controls. Treatment of LNCaP and C4-2B cells with androgens increased YKL40 expression, whereas treatment with an anti-androgen agent decreased the gene expression of YKL40 in androgen-sensitive LNCaP cells. Furthermore, knockdown of YKL40 significantly decreased invasion and migration of PCa cells, whereas overexpression rendered them more invasive and migratory, which was commensurate with an enhancement in the anchorage-independent growth of cells. To our knowledge, this study characterises the role of YKL40 for the first time in PCa. Together, these results suggest that YKL40 plays an important role in PCa progression and thus inhibition of YKL40 may be a potential therapeutic strategy for the treatment of PCa.

A random key genetic algorithm for live migration of multiple virtual machines in data centers

Live migration of multiple Virtual Machines (VMs) has become an integral management activity in data centers for power saving, load balancing and system maintenance. While state-of-the-art live migration techniques focus on the improvement of migration performance of an independent single VM, only a little has been investigated to the case of live migration of multiple interacting VMs. Live migration is mostly influenced by the network bandwidth and arbitrarily migrating a VM which has data inter-dependencies with other VMs may increase the bandwidth consumption and adversely affect the performances of subsequent migrations. In this paper, we propose a Random Key Genetic Algorithm (RKGA) that efficiently schedules the migration of a given set of VMs accounting both inter-VM dependency and data center communication network. The experimental results show that the RKGA can schedule the migration of multiple VMs with significantly shorter total migration time and total downtime compared to a heuristic algorithm.

From policy borrowing to implementation : an illuminative evaluation of learning and teaching in higher education in Australia (2002 to 2008)

This study documents and theorises the consequences of the 2003 Australian Government Reform Package focussed on learning and teaching in Higher Education during the period 2002 to 2008. This is achieved through the perspective of program evaluation and the methodology of illuminative evaluation. The findings suggest that the three national initiatives of that time, Learning and Teaching Performance Fund (LTPF), Australian Learning and Teaching Council (ALTC), and Australian Universities Quality Agency (AUQA), were successful in repositioning learning and teaching as a core activity in universities. However, there were unintended consequences brought about by international policy borrowing, when the short-lived nature of LTPF suggests a legacy of quality compliance rather than one of quality enrichment.

Convergent Media Policy

This chapter considers the implications of convergence for media policy from three perspectives. First, it discusses what have been the traditional concerns of media policy, and the challenges it faces, from the perspectives of public interest theories, economic capture theories, and capitalist state theories. Second, it looks at what media convergence involves, and some of the dilemmas arising from convergent media policy including: (1) determining who is a media company; (2) regulatory parity between ‘old’ and ‘new’ media; (3) treatment of similar media content across different platforms; (4) distinguishing ‘big media’ from user-created content; and (5) maintaining a distinction between media regulation and censorship of personal communication. Finally, it discusses attempts to reform media policy in light of these changes, including Australian media policy reports from 2011-12 including the Convergence Review, the Finkelstein Review of News Media, and the Australian Law Reform Commission’s National Classification Scheme Review. It concludes by arguing that ‘public interest’ approaches to media policy continue to have validity, even as they grapple with the complex question of how to understand the concept of influence in a convergent media environment.

Portrayals of child abuse scandals in the media in Australia and England : impacts on practice, policy, and systems

This article describes how the media have played a key role in placing the issue of child maltreatment and the problems associated with child protection high on public and political agendas over the last 50 years. It also describes how the influence of the media is far from unambiguous. Although the media has been crucial in bringing the problems into the open, it often does so in particular ways. In being so concerned with scandals and tragedies in a variety of institutionalized and community settings, the media have portrayed the nature of child maltreatment in ways which deflect attention from many of its core characteristics and causes. A focus on the media is important because of the power the media have to help transform the private into the public, but at the same time, to undermine trust, reputation, and legitimacy of the professionals working in the field. This concern is key for those working in the child protection field and has been a source of tension in public policy in both Australia and England for many years...

Public policy on corporate audit committees : case study evidence of current practice

Corporate failures and malpractices have led to an increasing emphasis on the governance role of audit committees. The Smith report Audit Committee Combined Code Guidance and the Higgs Review of the Role and Effectiveness of Non-Executive Directors (now incorporated in a Revised Combined Code) represent further attempts to strengthen corporate accountability in the UK. Although the regulatory focus on audit committees indicates confidence in their role as part of the solution to governance failures, questions remain about their efficacy in practice. Against the background of the publication of the Smith report and the wider reliance on audit committees in several countries to help improve corporate accountability, this paper provides research evidence, drawn from an ACCA-sponsored project, on the processes and effects of the audit committees in three UK companies. This study complements other research on audit committees by adopting a case study approach, in order to reflect the importance of investigating audit committee operations from within the organisation and to develop a closer understanding of audit committee impact than is available from generally observable data. The empirical evidence for the case studies was obtained from semi-structured interviews with personnel involved in the audit committee process, internal documents made available by the companies, and publicly available information, including annual reports.

Transition Pedagogy Handbook : A Good Practice Guide for Policy and Practice in the First Year Experience at QUT

This Handbook has been specifically designed for academic and professional staff responsible for managing first year students and curriculum and co-curricular programs at QUT. As well as presenting examples of good practice, the handbook provides a brief overview of QUT’s First Year Experience Program, a summary of QUT’s First Year Experience and Retention Policy and the Transition Pedagogy that frames both curricular and co-curricular activities. We hope you find this resource both useful and informative.

A policy model for access control using building information models

Building information models have created a paradigm shift in how buildings are built and managed by providing a dynamic repository for building data that is useful in many new operational scenarios. This change has also created an opportunity to use building information models as an integral part of security operations and especially as a tool to facilitate fine-grained access control to building spaces in smart buildings and critical infrastructure environments. In this paper, we identify the requirements for a security policy model for such an access control system and discuss why the existing policy models are not suitable for this application. We propose a new policy language extension to XACML, with BIM specific data types and functions based on the IFC specification, which we call BIM-XACML.

Chinese EFL students' response to an assessment policy change

In light of its documented potential for enhancing learning, formative assessment has been adopted across a range of educational contexts to improve the quality of education. The assessment innovation that the Chinese Ministry of Education (CMoE) proposed to College English in 2007 via the College English Curriculum Requirements (CECR) (CMoE, 2007), is an initiative of this kind. Considering the acknowledged influence of assessment on students’ learning, it is instructive to explore the ways in which Chinese university students respond to an assessment policy change of this magnitude, particularly as it positions them as more active learners, having the potential for increased agency and engagement in their English language learning and assessment practices. In order to explore the response of students to this assessment initiative, a case study was conducted in the context of a College English classroom. Data included an interview with a College English teacher and four students from her classes, and classroom observations and a survey of her two classes of 100 students. Analysis of the data reveals that Chinese students’ responses to the assessment policy change are influenced by a variety of sociocultural factors, including their previous English language learning and assessment experience and the extent to which they are willing to play the ‘assessment game’. These findings have implications for policy and practice.

Detoxification enzyme activities (CYP1A1 and GST) in the skin of humpback whales as a function of organochlorine burdens and migration status

The activities of glutathione-s-transferase (GST) and cytochrome P-450 1A1 (CYP1A1) enzymes were measured in freshly extracted epidermis of live-biopsied, migrating, southern hemisphere humpback whales (Megaptera novaeangliae). The two quantified enzyme activities did not correlate strongly with each other. Similarly, neither correlated strongly with any of the organochlorine compound groups previously measured in the superficial blubber of the sample biopsy core, likely reflecting the anticipated low levels of typical aryl-hydrocarbon receptor ligands. GST activity did not differ significantly between genders or between northward (early migration) or southward (late migration) migrating cohorts. Indeed, the inter-individual variability in GST measurements was relatively low. This observation raises the possibility that measured activities were basal activities and that GST function was inherently impacted by the fasting state of the sampled animals, as seen in other species. These results do not support the implementation of CYP1A1 or GST as effective biomarkers of organochlorine contaminant burdens in southern hemisphere populations of humpback whales as advocated for other cetacean species. Further investigation of GST activity in feeding versus fasting cohorts may, however, provide some insight into the fasting metabolism of these behaviourally adapted populations.

The glycosphingolipid P1 is an ovarian cancer-associated carbohydrate antigen involved in migration

Background The level of plasma-derived naturally circulating anti-glycan antibodies (AGA) to P1 trisaccharide has previously been shown to significantly discriminate between ovarian cancer patients and healthy women. Here we aim to identify the Ig class that causes this discrimination, to identify on cancer cells the corresponding P1 antigen recognised by circulating anti-P1 antibodies and to shed light into the possible function of this glycosphingolipid. Method An independent Australian cohort was assessed for the presence of anti-P1 IgG and IgM class antibodies using suspension array. Monoclonal and human derived anti-glycan antibodies were verified using three independent glycan-based immunoassays and flow cytometry-based inhibition assay. The P1 antigen was detected by LC-MS/MS and flow cytometry. FACS-sorted cell lines were studied on the cellular migration by colorimetric assay and real-time measurement using xCELLigence system. Results Here we show in a second independent cohort (n=155) that the discrimination of cancer patients is mediated by the IgM class of anti-P1 antibodies (P=0.0002). The presence of corresponding antigen P1 and structurally related epitopes in fresh tissue specimens and cultured cancer cells is demonstrated. We further link the antibody and antigen (P1) by showing that human naturally circulating and affinity-purified anti-P1 IgM isolated from patients ascites can bind to naturally expressed P1 on the cell surface of ovarian cancer cells. Cell-sorted IGROV1 was used to obtain two study subpopulations (P1-high, 66.1%; and P1-low, 33.3%) and observed that cells expressing high P1-levels migrate significantly faster than those with low P1-levels. Conclusions This is the first report showing that P1 antigen, known to be expressed on erythrocytes only, is also present on ovarian cancer cells. This suggests that P1 is a novel tumour-associated carbohydrate antigen recognised by the immune system in patients and may have a role in cell migration. The clinical value of our data may be both diagnostic and prognostic; patients with low anti-P1 IgM antibodies present with a more aggressive phenotype and earlier relapse.

The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells

The adhesion molecule L1, which is extensively characterized in the nervous system, is also expressed in dendritic cells (DCs), but its function there has remained elusive. To address this issue, we ablated L1 expression in DCs of conditional knockout mice. L1-deficient DCs were impaired in adhesion to and transmigration through monolayers of either lymphatic or blood vessel endothelial cells, implicating L1 in transendothelial migration of DCs. In agreement with these findings, L1 was expressed in cutaneous DCs that migrated to draining lymph nodes, and its ablation reduced DC trafficking in vivo. Within the skin, L1 was found in Langerhans cells but not in dermal DCs, and L1 deficiency impaired Langerhans cell migration. Under inflammatory conditions, L1 also became expressed in vascular endothelium and enhanced transmigration of DCs, likely through L1 homophilic interactions. Our results implicate L1 in the regulation of DC trafficking and shed light on novel mechanisms underlying transendothelial migration of DCs. These observations might offer novel therapeutic perspectives for the treatment of certain immunological disorders.