A collagen prolyl 4-hydroxylase inhibitor reduces adhesions after tendon injury

Collagen synthesis inhibition potentially can reduce adhesion formation after tendon injury but also may affect cutaneous wound healing. We hypothesized that a novel orally administered collagen synthesis inhibitor (CPHI-I) would substantially reduce flexor tendon adhesions after injury, without any clinically important effect on cutaneous wound healing. The experiments were performed in a rat model with an in-continuity crush injury model in the rat hindfoot flexor tendon to provoke adhesion formation. Assays of dermal collagen production and the rate of healing of an excised wound were performed to assess cutaneous wound healing. Animals in the treatment groups received CPHI-I for 1, 2, or 6 weeks and were assessed at either 2 or 6 weeks. The work of flexion in the injured digit was reduced in the CPHI-I-treated animals compared with control animals, (0.188 J versus 0.0307 J at 2 weeks, and 0.0231 J versus 0.0331 J at 6 weeks) The cutaneous wound healing rate was similar in all animals, but dermal collagen synthesis was reduced in the treated animals. The CPHI-I seems to reduce tendon adhesion, and although collagen synthesis was reduced in cutaneous wounds, CPHI-I did not retard wound healing.

Applying Enterprise Architecture to Business Networks

Globalization, financial deregulation, economic turmoil, and technology breakthroughs are profoundly exposing organizations to business networks. Engaging these networks requires explicit planning from the strategic level down to the operational level of an organization, which significantly affects organizational artefacts such as business services, processes, and resources. Although enterprise architecture (EA) aligns business and IT aspects of organizational systems, previous applications of EA have not comprehensively addressed a methodological framework for planning. In the context of business networks, this study seeks to explore the application of EA for business network planning where it builds upon relevant and well-established prescriptive and descriptive aspects of EA. Prescriptive aspects include integrated models of services, business processes, and resources among other organizational artefacts, at both business and IT levels. Descriptive aspects include ontological classifications of business functionality, which allow EA models to be aligned semantically to organizational artefacts and, ultimately higher-level business strategy. A prominent approach for capturing descriptive aspects of EA is business capability modelling. In order to explore and develop the illustrative extensions of EA through capability modelling, a list of requirements (capability dimensions) for business network planning will be identified and validated through a revelatory case study encompassing different business network manifestations, or situations. These include virtual organization, liquid workforce, business network orchestration, and headquarters-subsidiary. The use of artefacts, conventionally, modelled through EA will be considered in these network situations. Two general considerations for EA extensions are explored for the identified requirements at the level of the network: extension of artefacts through the network and alignment of network level artefacts with individual organization artefacts. The list of requirements provides the basis for a constructivist extension of EA in the following ways. Firstly, for descriptive aspects, it offers constructivist insights to guide extensions for particular EA techniques and concepts. Secondly, for prescriptive aspects it defines a set of capability dimensions, which improve the analysis and assessment of organization capabilities for business network situations.

Interchangeability of infrared and conductive devices for the measurement of human skin temperature

This thesis is a comparative investigation of the methodology applied to human skin temperature measurement. The findings of this thesis suggest that clinical and significant differences exist between conductive and infrared devices which are commonly employed in the assessment of human skin temperature. These significant differences could potentially influence the interpretation of results, diagnosis and therefore treatment outcomes for health, clinical and exercise science applications.

Clinicopathological relevance of BRAF mutations in human cancer

BRAF represents one of the most frequently mutated protein kinase genes in human tumours. The mutation is commonly tested in pathology practice. BRAF mutation is seen in melanoma, papillary thyroid carcinoma (including papillary thyroid carcinoma arising from ovarian teratoma), ovarian serous tumours, colorectal carcinoma, gliomas, hepatobiliary carcinomas and hairy cell leukaemia. In these cancers, various genetic aberrations of the BRAF proto-oncogene, such as different point mutations and chromosomal rearrangements, have been reported. The most common mutation, BRAF V600E, can be detected by DNA sequencing and immunohistochemistry on formalin fixed, paraffin embedded tumour tissue. Detection of BRAF V600E mutation has the potential for clinical use as a diagnostic and prognostic marker. In addition, a great deal of research effort has been spent in strategies inhibiting its activity. Indeed, recent clinical trials involving BRAF selective inhibitors exhibited promising response rates in metastatic melanoma patients. Clinical trials are underway for other cancers. However, cutaneous side effects of treatment have been reported and therapeutic response to cancer is short-lived due to the emergence of several resistance mechanisms. In this review, we give an update on the clinical pathological relevance of BRAF mutation in cancer. It is hoped that the review will enhance the direction of future research and assist in more effective use of the knowledge of BRAF mutation in clinical practice.

Academic librarians' varying experiences of archives : a phenomenographic study

This article reports on a study investigating academic librarians' varying experiences of archives in order to promote understanding and communication among librarians and archivists. A qualitative, phenomenographic approach was adopted for the study. Three different ways of experiencing archives were identified from analysis of interviews. Archives may be experienced by academic librarians as 1) a place which protects collections; 2) resources to be used in accomplishing tasks such as teaching, research, or outreach; or 3) manifestations of politics. The third way of experiencing archives is the most complex, incorporating both the other experiences. The results of this study may help librarians, especially academic librarians, and archivists communicate more clearly on joint projects involving archival collections thereby enabling more collaboration.

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.

Ramipril - improving exercise tolerance in intermittent claudication?

Peripheral artery disease (PAD) is one of the most common manifestations of systemic atherosclerosis. It is estimated that 10-15% of the general population is affected by PAD, whereby the narrowed arteries lead to reduced blood flow to the extremeties - particularly the legs. While many people have mild or no systems with PAD, approximately one-third of people experience intermittent claudication (IC).

Autologous human kidney proximal tubule epithelial cells (PTEC) modulate dendritic cell (DC), T cell and B cell responses

This is a comprehensive study of human kidney proximal tubular epithelial cells (PTEC) which are known to respond to and mediate the pathological process of a range of kidney diseases. It identifies various molecules expressed by PTEC and how these molecules participate in down-regulating the inflammatory process, thereby highlighting the clinical potential of these molecules to treat various kidney diseases. In the disease state, PTEC gain the ability to regulate the immune cell responses present within the interstitium. This down-regulation is a complex interaction of contact dependent/independent mechanisms involving various immuno-regulatory molecules including PD-L1, sHLA-G and IDO. The overall outcome of this down-regulation is suppressed DC maturation, decreased number of antibody producing B cells and low T cell responses. These manifestations within a clinical setting are expected to dampen the ongoing inflammation, preventing the damage caused to the kidney tissue.

Social media(tion) and the reshaping of public/private boundaries in employment relations

Tensions surrounding social media in the employment relationship are increasingly evident in the media, public rhetoric, and courts and employment tribunals. Yet the underlying causes and dimensions of these tensions have remained largely unexplored. This article firstly reviews the available literature addressing social media and employment, outlining three primary sources of contestation: profiling, disparaging posts and blogs, and private use of social media during work time. In each area, the key dynamics and underlying concerns of the central actors involved are identified. The article then seeks to canvas explanations for these forms of contestation associated with social media at work. It is argued that the architecture of social media disrupts traditional relations in organisational life by driving employer and employee actions that (re)shape and (re)constitute the boundaries between public and private spheres. Although employers and employees are using the same social technologies, their respective concerns about and points of entry to these technologies, in contrast to traditional manifestations of conflict and resistance, are asymmetric. The article concludes with a representational summary of the relative legitimacy of concerns for organisational actors and outlines areas for future research.

Workplace sexual harassment at the margins

Men are overwhelmingly responsible for sexual harassment against women in the workplace. However, the literature also points to less typical manifestations, including sexual harassment by men of other men and by women of men or other women. This article examines these atypical forms of sexual harassment, drawing on a census of all formal sexual harassment complaints lodged with Australian equal opportunity commissions over a six-month period. The analysis reveals some important distinctions and similarities across groups of atypical complaints, as well as between atypical groups and ‘classic’ sexual harassment complaints where men harass women. The article contributes to the relatively undeveloped literature on these less visible forms of sexual harassment and highlights both theoretical and pragmatic challenges in better understanding workplace sexual harassment ‘at the margins’.

Manipulating the data: Teaching and NAPLAN in the control society

High-stakes testing is changing what it means to be a ‘good teacher’ in the contemporary school. This paper uses Deleuze and Guattari's ideas on the control society and dividuation in the context of National Assessment Program Literacy and Numeracy (NAPLAN) testing in Australia to suggest that the database generates new understandings of the ‘good teacher’. Media reports are used to look at how teachers are responding to the high-stakes database through manipulating the data. This article argues that manipulating the data is a regrettable, but logical, response to manifestations of teaching where only the data counts.

A qualitative exploration of parental experiences of stigma while living with HIV in Bangladesh

With much of the focus on the “risk” groups, families have often been less studied in HIV research. Further, because of a focus on the aetiology and epidemiology of HIV, the social impacts associated with HIV on families and neighbours are sometimes overlooked. This study examined parental experiences of stigma and discrimination while living with HIV within a family context in Bangladesh. A qualitative research design using a grounded theory approach was used for this research. Data was collected through in-depth interviews with 19 HIV-positive parents, recruited with the support of two self-help groups of HIV-positive people, in two settings namely Khulna and Dhaka in Bangladesh. The findings indicate that HIV-positive parents held the view that they continue to experience significant stigma and their narratives clearly show how this affected them and their children. A range of informal practices were enacted in everyday contexts by extended family and community members to identify, demarcate and limit the social interaction of HIV-positive parents. Parents highlighted a number of factors including negative thoughts and behaviours, rejection, isolation and derogatory remarks as manifestations of stigma and discrimination, impacting upon them and their children because of their association with HIV.

Neo-Piagetian Theory and the novice programmer

This PhD project studied the genetic epistemology of novice programmers, and provides empirical evidence that the development of programming skills can be described using the neo-Piagetian cognitive development framework. The thesis identifies the manifestations of each of the early neo-Piagetian stages of development in the programming domain – that is: sensorimotor, preoperational and concrete operational. This research informs not only tertiary pedagogy, but teaching and learning of computer programming in any setting. It will enable educators to (a) identify the developmental stage of their students, (b) provide stage-appropriate learning resources and (c) assist students in transitioning to the next more mature stage of reasoning.

Resilience: A new integrative approach to health and mental health research

We know from anecdote and research, science and art, that human resilience is a powerful, seemingly ubiquitous force. What is needed is a better understanding of the properties, variations, and applications of that concept to health and well-being. In this paper we put forth two definitions of resilience: Sustainability of purpose in the face of stress, and recovery from adversity. We review current thinking in the social sciences on the nature of biological, psychological and socio-community processes that may confer resilience. In doing so, we encourage greater attention to aspects of biopsychosocial resourcefulness as a dimension of influence on health and mental health distinct from measures of risk found in standard models of public health inquiry. Multi-level, longitudinal, and intervention methods are advocated for research and applications of the concept with conceptual guidelines for the examination of laboratory, diary, and community indicator data on manifestations of resilience across the life span.

The effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis

Objective. To analyze the effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis (AS). Methods. Three hundred sixty- three white British AS patients were studied; 149 were carefully assessed for a range of clinical manifestations, and disease severity was assessed using a structured questionnaire. Limited HLA class I typing and complete HLA-DR typing were performed using DNA-based methods. HLA data from 13,634 healthy white British bone marrow donors were used for comparison. Results. A significant association between DR1 and AS was found, independent of HLA-B27 (overall odds ratio [OR] 1.4, 95% confidence interval [95% CI] 1.1-1.8, P = 0.02; relative risk [RR] 2.7, 95% CI 1.5-4.8, P = 6 x 10-4 among homozygotes; RR 2.1, 95% CI 1.5-2.8, P = 5 x 10-6 among heterozygotes). A large but weakly significant association between DR8 and AS was noted, particularly among DR8 homozygotes (RR 6.8, 95% CI 1.6-29.2, P = 0.01 among homozygotes; RR 1.6, 95% CI 1.0-2.7, P = 0.07 among heterozygotes). A negative association with DR12 (OR 0.22, 95% CI 0.09-0.5, P = 0.001) was noted. HLA-DR7 was associated with younger age at onset of disease (mean age at onset 18 years for DR7-positive patients and 23 years for DR7-negative patients; Z score 3.21, P = 0.001). No other HLA class I or class H associations with disease severity or with different clinical manifestations of AS were found. Conclusion. The results of this study suggest that HLA-DR genes may have a weak effect on susceptibility to AS independent of HLA-B27, but do not support suggestions that they affect disease severity or different clinical manifestations.