Histological and morphometric lesions in the pre-clinical, developmental phase of insulin-induced laminitis in Standardbred horses

Lamellar pathology in experimentally-induced equine laminitis associated with euglycaemic hyperinsulinaemia is substantial by the acute, clinical phase (∼48 h post-induction). However, lamellar pathology of the developmental, pre-clinical phase requires evaluation. The aim of this study was to analyse lamellar lesions both qualitatively and quantitatively, 6, 12 and 24 h after the commencement of hyperinsulinaemia. Histological and histomorphometrical analyses of lamellar pathology at each time-point included assessment of lamellar length and width, epidermal cell proliferation and death, basement membrane (BM) pathology and leucocyte infiltration. Archived lamellar tissue from control horses and those with acute, insulin-induced laminitis (48 h) was also assessed for cellular proliferative activity by counting the number of cells showing positive nuclear immuno labelling for TPX2. Decreased secondary epidermal lamellar (SEL) width and increased histomorphological evidence of SEL epidermal basal (and supra-basal) cell death occurred early in disease progression (6 h). Increased cellular proliferation in SELs, infiltration of the dermis with small numbers of leucocytes and BM damage occurred later (24 and 48 h). Some lesions, such as narrowing of the SELs, were progressive over this time period (6–48 h). Cellular pathology preceded leucocyte infiltration and BM pathology, indicating that the latter changes may be secondary or downstream events in hyperinsulinaemic laminitis.

The feral horse foot. Part B : radiographic, gross visual and histopathological parameters of foot health in 100 Australian feral horses

Background It has been proposed that the feral horse foot is a benchmark model for foot health in horses. However, the foot health of feral horses has not been formally investigated. Objectives To investigate the foot health of Australian feral horses and determine if foot health is affected by environmental factors, such as substrate properties and distance travelled. Methods Twenty adult feral horses from five populations (n = 100) were investigated. Populations were selected on the basis of substrate hardness and the amount of travel typical for the population. Feet were radiographed and photographed, and digital images were surveyed by two experienced assessors blinded to each other's assessment and to the population origin. Lamellar samples from 15 feet from three populations were investigated histologically for evidence of laminitis. Results There was a total of 377 gross foot abnormalities identified in 100 left forefeet. There were no abnormalities detected in three of the feet surveyed. Each population had a comparable prevalence of foot abnormalities, although the type and severity of abnormality varied among populations. Of the three populations surveyed by histopathology, the prevalence of chronic laminitis ranged between 40% and 93%. Conclusions Foot health appeared to be affected by the environment inhabited by the horses. The observed chronic laminitis may be attributable to either nutritional or traumatic causes. Given the overwhelming evidence of suboptimal foot health, it may not be appropriate for the feral horse foot to be the benchmark model for equine foot health.

The confidence of speech-language pathology students regarding communicating with people with aphasia

Background Aphasia is an acquired language disorder that can present a significant barrier to patient involvement in healthcare decisions. Speech-language pathologists (SLPs) are viewed as experts in the field of communication. However, many SLP students do not receive practical training in techniques to communicate with people with aphasia (PWA) until they encounter PWA during clinical education placements. Methods This study investigated the confidence and knowledge of SLP students in communicating with PWA prior to clinical placements using a customised questionnaire. Confidence in communicating with people with aphasia was assessed using a 100-point visual analogue scale. Linear, and logistic, regressions were used to examine the association between confidence and age, as well as confidence and course type (graduate-entry masters or undergraduate), respectively. Knowledge of strategies to assist communication with PWA was examined by asking respondents to list specific strategies that could assist communication with PWA. Results SLP students were not confident with the prospect of communicating with PWA; reporting a median 29-points (inter-quartile range 17–47) on the visual analogue confidence scale. Only, four (8.2%) of respondents rated their confidence greater than 55 (out of 100). Regression analyses indicated no relationship existed between confidence and students‘ age (p = 0.31, r-squared = 0.02), or confidence and course type (p = 0.22, pseudo r-squared = 0.03). Students displayed limited knowledge about communication strategies. Thematic analysis of strategies revealed four overarching themes; Physical, Verbal Communication, Visual Information and Environmental Changes. While most students identified potential use of resources (such as images and written information), fewer students identified strategies to alter their verbal communication (such as reduced speech rate). Conclusions SLP students who had received aphasia related theoretical coursework, but not commenced clinical placements with PWA, were not confident in their ability to communicate with PWA. Students may benefit from an educational intervention or curriculum modification to incorporate practical training in effective strategies to communicate with PWA, before they encounter PWA in clinical settings. Ensuring students have confidence and knowledge of potential communication strategies to assist communication with PWA may allow them to focus their learning experiences in more specific clinical domains, such as clinical reasoning, rather than building foundation interpersonal communication skills.

Factors influencing research engagement : research interest, confidence and experience in an Australian speech-language pathology workforce

Background Recent initiatives within an Australia public healthcare service have seen a focus on increasing the research capacity of their workforce. One of the key initiatives involves encouraging clinicians to be research generators rather than solely research consumers. As a result, baseline data of current research capacity are essential to determine whether initiatives encouraging clinicians to undertake research have been effective. Speech pathologists have previously been shown to be interested in conducting research within their clinical role; therefore they are well positioned to benefit from such initiatives. The present study examined the current research interest, confidence and experience of speech language pathologists (SLPs) in a public healthcare workforce, as well as factors that predicted clinician research engagement. Methods Data were collected via an online survey emailed to an estimated 330 SLPs working within Queensland, Australia. The survey consisted of 30 questions relating to current levels of interest, confidence and experience performing specific research tasks, as well as how frequently SLPs had performed these tasks in the last 5 years. Results Although 158 SLPs responded to the survey, complete data were available for only 137. Respondents were more confident and experienced with basic research tasks (e.g., finding literature) and less confident and experienced with complex research tasks (e.g., analysing and interpreting results, publishing results). For most tasks, SLPs displayed higher levels of interest in the task than confidence and experience. Research engagement was predicted by highest qualification obtained, current job classification level and overall interest in research. Conclusions Respondents generally reported levels of interest in research higher than their confidence and experience, with many respondents reporting limited experience in most research tasks. Therefore SLPs have potential to benefit from research capacity building activities to increase their research skills in order to meet organisational research engagement objectives. However, these findings must be interpreted with the caveats that a relatively low response rate occurred and participants were recruited from a single state-wide health service, and therefore may not be representative of the wider SLP workforce.

Bcl-2 genes and growth factors in the pathology of ischaemic acute renal failure

For the past decade, an attempt has been made by many research groups to define the roles of the growing number of Bcl-2 gene family proteins in the apoptotic process. The Bcl-2 family consists of pro-apoptotic (or cell death) and anti-apoptotic (or cell survival) genes and it is the balance in expression between these gene lineages that may determine the death or survival of a cell. The majority of studies have analysed the role/s of the Bcl-2 genes in cancer development. Equally important is their role in normal tissue development, homeostasis and non-cancer disease states. Bcl-2 is crucial for normal development in the kidney, with a deficiency in Bcl-2 producing such malformation that renal failure and death result. As a corollary, its role in renal disease states in the adult has been sought. Ischaemia is one of the most common causes of both acute and chronic renal failure. The section of the kidney that is most susceptible to ischaemic damage is the outer zone of the outer medulla. Within this zone the proximal tubules are most sensitive and often die by necrosis or desquamate. In the distal nephron, apoptosis is the more common form of cell death. Recent results from our laboratory have indicated that ischaemia-induced acute renal failure is associated with up-regulation of two anti-apoptotic Bcl-2 proteins (Bcl-2 and Bcl-XL) in the damaged distal tubule and occasional up-regulation of Bax in the proximal tubule. The distal tubule is a known reservoir for several growth factors important to renal growth and repair, such as insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF). One of the likely possibilities for the anti-cell death action of the Bcl-2 genes is that the protected distal cells may be able to produce growth factors that have a further reparative or protective role via an autocrine mechanism in the distal segment and a paracrine mechanism in the proximal cells. Both EGF and IGF-1 are also up-regulated in the surviving distal tubules and are detected in the surviving proximal tubules, where these growth factors are not usually synthesized. As a result, we have been using in vitro methods to test: (i) the relative sensitivities of renal distal and proximal epithelial cell populations to injury caused by mechanisms known to act in ischaemia-reperfusion; (ii) whether a Bcl-2 anti-apoptotic mechanism acts in these cells; and (iii) whether an autocrine and/or paracrine growth factor mechanism is initiated. The following review discusses the background to these studies as well as some of our preliminary results.

Immunization with a MOMP-based vaccine protects mice against a Pulmonary Chlamydia challenge and identifies a disconnection between infection and pathology

Chlamydia pneumoniae is responsible for up to 20% of community acquired pneumonia and can exacerbate chronic inflammatory diseases. As the majority of infections are either mild or asymptomatic, a vaccine is recognized to have the greatest potential to reduce infection and disease prevalence. Using the C. muridarum mouse model of infection, we immunized animals via the intranasal (IN), sublingual (SL) or transcutaneous (TC) routes, with recombinant chlamydial major outer membrane protein (MOMP) combined with adjuvants CTA1-DD or a combination of cholera toxin/CpG-oligodeoxynucleotide (CT/CpG). Vaccinated animals were challenged IN with C. muridarum and protection against infection and pathology was assessed. SL and TC immunization with MOMP and CT/CpG was the most protective, significantly reducing chlamydial burden in the lungs and preventing weight loss, which was similar to the protection induced by a previous live infection. Unlike a previous infection however, these vaccinations also provided almost complete protection against fibrotic scarring in the lungs. Protection against infection was associated with antigen-specific production of IFNγ, TNFα and IL-17 by splenocytes, however, protection against both infection and pathology required the induction of a similar pro-inflammatory response in the respiratory tract draining lymph nodes. Interestingly, we also identified two contrasting vaccinations capable of preventing infection or pathology individually. Animals IN immunized with MOMP and either adjuvant were protected from infection, but not the pathology. Conversely, animals TC immunized with MOMP and CTA1-DD were protected from pathology, even though the chlamydial burden in this group was equivalent to the unimmunized controls. This suggests that the development of pathology following an IN infection of vaccinated animals was independent of bacterial load and may have been driven instead by the adaptive immune response generated following immunization. This identifies a disconnection between the control of infection and the development of pathology, which may influence the design of future vaccines.

Toll-like receptor and pro-inflammatory cytokine expression during prolonged hyperinsulinaemia in horses : implications for laminitis

Equine laminitis, a disease of the lamellar structure of the horse’s hoof, can be incited by numerous factors that include inflammatory and metabolic aetiologies. However, the role of inflammation in hyperinsulinaemic laminitis has not been adequately defined. Tolllike receptor (TLR) activation results in up-regulation of inflammatory pathways and the release of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-�), and may be a pathogenic factor in laminitis. The aim of this study was to determine whether TLR4 expression and subsequent pro-inflammatory cytokine production is increased in lamellae and skeletal muscle during equine hyperinsulinaemia. Standardbred horses were treated with either a prolonged, euglycaemic hyperinsulinaemic clamp (p-EHC) or a prolonged, glucose infusion (p-GI), which induced marked and moderate hyperinsulinaemia, respectively. Age-matched control horses were treated simultaneously with a balanced electrolyte solution. Treated horses developed clinical (p-EHC) or subclinical (p-GI) laminitis, whereas controls did not. Skeletal muscle and lamellar protein extracts were analysed by Western blotting for TLR4, IL-6, TNF-� and suppressor of cytokine signalling 3 (SOCS3) expression. Lamellar protein expression of TLR4 and TNF-�, but not IL-6, was increased by the p-EHC, compared to control horses. A significant positive correlation was found between lamellar TLR4 and SOCS3. Skeletal muscle protein expression of TLR4 signalling parameters did not differ between control and p-EHC-treated horses. Similarly, the p-GI did not result in up-regulation of lamellar protein expression of any parameter. The results suggest that insulin-sensitive tissues may not accurately reflect lamellar pathology during hyperinsulinaemia. While TLR4 is present in the lamellae, its activation appears unlikely to contribute significantly to the developmental pathogenesis of hyperinsulinaemic laminitis. However, inflammation may have a role to play in the later stages (e.g., repair or remodelling) of the disease.

The impact of OCR accuracy on automated cancer classification of pathology reports

Objective To evaluate the effects of Optical Character Recognition (OCR) on the automatic cancer classification of pathology reports. Method Scanned images of pathology reports were converted to electronic free-text using a commercial OCR system. A state-of-the-art cancer classification system, the Medical Text Extraction (MEDTEX) system, was used to automatically classify the OCR reports. Classifications produced by MEDTEX on the OCR versions of the reports were compared with the classification from a human amended version of the OCR reports. Results The employed OCR system was found to recognise scanned pathology reports with up to 99.12% character accuracy and up to 98.95% word accuracy. Errors in the OCR processing were found to minimally impact on the automatic classification of scanned pathology reports into notifiable groups. However, the impact of OCR errors is not negligible when considering the extraction of cancer notification items, such as primary site, histological type, etc. Conclusions The automatic cancer classification system used in this work, MEDTEX, has proven to be robust to errors produced by the acquisition of freetext pathology reports from scanned images through OCR software. However, issues emerge when considering the extraction of cancer notification items.

Classification of pathology reports for cancer registry notifications

Objective: To develop a system for the automatic classification of pathology reports for Cancer Registry notifications. Method: A two pass approach is proposed to classify whether pathology reports are cancer notifiable or not. The first pass queries pathology HL7 messages for known report types that are received by the Queensland Cancer Registry (QCR), while the second pass aims to analyse the free text reports and identify those that are cancer notifiable. Cancer Registry business rules, natural language processing and symbolic reasoning using the SNOMED CT ontology were adopted in the system. Results: The system was developed on a corpus of 500 histology and cytology reports (with 47% notifiable reports) and evaluated on an independent set of 479 reports (with 52% notifiable reports). Results show that the system can reliably classify cancer notifiable reports with a sensitivity, specificity, and positive predicted value (PPV) of 0.99, 0.95, and 0.95, respectively for the development set, and 0.98, 0.96, and 0.96 for the evaluation set. High sensitivity can be achieved at a slight expense in specificity and PPV. Conclusion: The system demonstrates how medical free-text processing enables the classification of cancer notifiable pathology reports with high reliability for potential use by Cancer Registries and pathology laboratories.

Good practice report : clinical teaching

Clinical experience, or experience in the ‘real world’ of practice, is a fundamental component of many health professional courses. It often involves students undertaking practical experience in clinical workplace settings, typically referred to as clinical placements, under the supervision of health professionals. Broadly speaking, the role of clinical supervisors, or teachers, is aimed at assisting students to integrate the theoretical and skills based components of the curriculum within the context of patient/client care (Erstzen et al 2009). Clinical experience also provides students with the opportunity to assimilate the attitudes, values and skills which they require to become appropriately skilled professionals in the environments in which they will eventually practise. However, clinical settings are particularly challenging learning environments for students. Unlike classroom learning, students in the clinical setting frequently find themselves involved in unplanned and often complex activities with patients and other health care providers, being supervised by a variety of clinical staff who have very different methods and styles of teaching, and negotiating bureaucratic or hierarchical structures in busy clinical workplaces where they may only be spending a limited amount of time. Kilminster et al (2007) also draw attention to tensions that may exist between the learning needs of students and the provision of quality care or need to prevent harm to the patient (e.g. Elkind et al 2007). All of these factors complicate the realisation of clinical education goals and underscore the need for effective clinical teaching practices that maximise student learning in clinical environments. This report provides a summary of work that has been achieved in relation to ALTC projects and fellowships associated with clinical teaching, and a review of scholarly publications relevant to this field. The report also makes recommendations based on issues identified and/or where further work is indicated. The projects and fellowships reviewed cover a range of discipline areas including Biology, Paramedic Practice, Clinical Exercise Physiology, Occupational Therapy, Speech Pathology, Physiotherapy, Pharmacy, Nursing and Veterinary Science. The main areas of focus cover issues related to curriculum, particularly in relation to industry expectations of ‘work-ready’ graduates and the implications for theoretical and practical, or clinical preparation; development of competency assessment tools that are nationally applicable across discipline-specific courses; and improvement of clinical learning through strategies targeting the clinical learning environment, building the teaching capacity of clinical supervisors and/or enhancing the clinical learning/teaching process.

Second ESMO consensus conference on lung cancer : pathology and molecular biomarkers for non-small-cell lung cancer

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The Second ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on management of patients with nonsmall- cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, early stage disease, locally advanced disease and advanced (metastatic) disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on recommendations for pathology and molecular biomarkers in relation to the diagnosis of lung cancer, primarily non-small-cell carcinomas.

Imaginging the good Indigenous citizen : race war and the pathology of partiarchal white sovereignty

In June 2007, the Australian federal government sent military and policy into Indigenous communities in the Northern Territory on the premise that sexual abuse of children was rampant and a national crisis. This article draws on Foucault’s work on sovereignty and rights to argue that patriarchal white sovereignty as a regime of power deploys a discourse of pathology in the exercising of sovereign right to subjugate and discipline Indigenous people as good citizens.

Oldest pathology in a tetrapod bone illuminates the origin of terrestrial vertebrates

The origin of terrestrial tetrapods was a key event in vertebrate evolution, yet how and when it occurred remains obscure, due to scarce fossil evidence. Here, we show that the study of palaeopathologies, such as broken and healed bones, can help elucidate poorly understood behavioural transitions such as this. Using high-resolution finite element analysis, we demonstrate that the oldest known broken tetrapod bone, a radius of the primitive stem tetrapod Ossinodus pueri from the mid-Viséan (333 million years ago) of Australia, fractured under a high-force, impact-type loading scenario. The nature of the fracture suggests that it most plausibly occurred during a fall on land. Augmenting this are new osteological observations, including a preferred directionality to the trabecular architecture of cancellous bone. Together, these results suggest that Ossinodus, one of the first large (>2m length) tetrapods, spent a significant proportion of its life on land. Our findings have important implications for understanding the temporal, biogeographical and physiological contexts under which terrestriality in vertebrates evolved. They push the date for the origin of terrestrial tetrapods further back into the Carboniferous by at least two million years. Moreover, they raise the possibility that terrestriality in vertebrates first evolved in large tetrapods in Gondwana rather than in small European forms, warranting a re-evaluation of this important evolutionary event.