Influence of inflow turbulence in shock-wave/turbulent-boundary-layer interaction computations

The influence of inflow turbulence on the results of Favre–Reynolds-averaged Navier–Stokes computations of supersonic oblique-shock-wave/turbulent-boundary-layer interactions (shock-wave Mach-number MSW ∼2.9), using seven-equation Reynolds-stress model turbulence closures, is studied. The generation of inflow conditions (and the initialization of the flowfield) for mean flow, Reynolds stresses, and turbulence length scale, based on semi-analytic grid-independent boundary-layer profiles, is described in detail. Particular emphasis is given to freestream turbulence intensity and length scale. The influence of external-flow turbulence intensity is studied in detail both for flat-plate boundary-layer flow and for a compression-ramp interaction with large separation. It is concluded that the Reynolds-stress model correctly reproduces the effects of external flow turbulence.

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.

Blast induced ground shock effects on pile foundations

Due to increased number of terrorist attacks in recent years, loads induced by explosions need to be incorporated in building designs. For safer performance of a structure, its foundation should have sufficient strength and stability. Therefore, prior to any reconstruction or rehabilitation of a building subjected to blast, it is important to examine adverse effects on the foundation caused by blast induced ground shocks. This paper evaluates the effects of a buried explosion on a pile foundation. It treats the dynamic response of the pile in saturated sand, using explicit dynamic nonlinear finite element software LS-DYNA. The blast induced wave propagation in the soil and the horizontal deformation of pile are presented and the results are discussed. Further, a parametric study is carried out to evaluate the effect of varying the explosive shape on the pile response. This information can be used to evaluate the vulnerability of piled foundations to credible blast events as well as develop guidance for their design.

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.

Advanced arterial blood gas analysis in septic shock : a Singaporean nursing case review.

Introduction The admission to the Intensive Care Unit with a diagnosis of sepsis and/or septic shock is not uncommon. The aim of this article is to present a nursing case review of a patient admitted to the intensive care unit with a diagnosis of septic shock and the use of bedside acid–base formulae to inform clinical decision making. Method We chose to use a case review. This method is useful in reporting unusual or rare cases and is typically seen more in medicine than in nursing. Discussion The gentleman in question was a self-presentation with a short history of fever and worsening shortness of breath. His condition worsened where he required admission to the intensive care unit. The use of ‘advanced’ acid–base interpretation to guide his nursing care provided a platform from which to advance a deeper understanding of the intricacies the critically ill patient often presents. Conclusion The use of case review is enlightening in understanding the disease process and the decision-making that accompanies this. The lessons learnt are applicable to a wider nursing audience because understanding acid–base physiology is beneficial in supporting and advancing critical care nursing practice.

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.

The heat shock protein 90 inhibitor, 17-allylamino-17- demethoxygeldanamycin, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line

Breast cancer metastasis to the bone occurs frequently, causing numerous complications including severe pain, fracture, hypercalcemia, and paralysis. Despite its prevalence and severity, few effective therapies exist. To address this, we examined whether the heat shock protein 90 (Hsp90) inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), would be efficacious in inhibiting breast cancer metastasis to bone. Utilizing the human breast cancer subline, MDA-MB-231SA, previously in vivo selected for its enhanced ability to generate osteolytic bone lesions, we determined that 17-AAG potently inhibited its in vitro proliferation and migration. Moreover, 17-AAG significantly reduced MDA-MB-231SA tumor growth in the mammary-fat pad of nude mice. Despite these findings, 17-AAG enhanced the incidence of bone metastasis and osteolytic lesions following intracardiac inoculation in the nude mouse. Consistent with these findings, 17-AAG enhanced osteoclast formation 2- to 4-fold in mouse bone marrow/osteoblast cocultures, receptor activator of nuclear factor κB ligand (BANKL)-stimulated bone marrow, and RAW264.7 cell models of in vitro osteoclastogenesis. Moreover, the drug enhanced osteoclastogenesis in human cord blood progenitor cells, demonstrating that its effects were not limited to mouse models. In addition to 17-AAG, other Hsp90 inhibitors, such as radicicol and herbimycin A, also enhanced osteoclastogenesis. A pro-osteolytic action of 17-AAG independent of tumor presence was also determined in vivo, in which 17-AAG-treated tumor-naive mice had reduced trabecular bone volume with an associated increase in osteoclast number. Thus, HSP90 inhibitors can stimulate osteoclast formation, which may underlie the increased incidence of osteolysis and skeletal tumor incidence causedby 17-AAG in vivo. These data suggest an important contraindication to the Hsp90 targeted cancer therapy currently undergoing clinical trial.

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.

Interleukin-23 mediates the intestinal response to microbial β-1,3-glucan and the development of spondyloarthritis pathology in SKG mice

Objective Spondyloarthritides (SpA) occur in 1% of the population and include ankylosing spondylitis (AS) and arthropathy of inflammatory bowel disease (IBD), with characteristic spondylitis, arthritis, enthesitis, and IBD. Genetic studies implicate interleukin-23 (IL-23) receptor signaling in the development of SpA and IBD, and IL-23 overexpression in mice is sufficient for enthesitis, driven by entheseal-resident T cells. However, in genetically prone individuals, it is not clear where IL-23 is produced and how it drives the SpA syndrome, including IBD or subclinical gut inflammation of AS. Moreover, it is unclear why specific tissue involvement varies between patients with SpA. We undertook this study to determine the location of IL-23 production and its role in SpA pathogenesis in BALB/c ZAP-70W163C-mutant (SKG) mice injected intraperitoneally with β-1,3-glucan (curdlan). Methods Eight weeks after curdlan injection in wild-type or IL-17A-/- SKG or BALB/c mice, pathology was scored in tissue sections. Mice were treated with anti-IL-23 or anti-IL-22. Cytokine production and endoplasmic reticulum (ER) stress were determined in affected organs. Results In curdlan-treated SKG mice, arthritis, enthesitis, and ileitis were IL-23 dependent. Enthesitis was specifically dependent on IL-17A and IL-22. IL-23 was induced in the ileum, where it amplified ER stress, goblet cell dysfunction, and proinflammatory cytokine production. IL-17A was pathogenic, while IL-22 was protective against ileitis. IL-22+CD3- innate-like cells were increased in lamina propria mononuclear cells of ileitis-resistant BALB/c mice, which developed ileitis after curdlan injection and anti-IL-22. Conclusion In response to systemic β-1,3-glucan, intestinal IL-23 provokes local mucosal dysregulation and cytokines driving the SpA syndrome, including IL-17/IL-22-dependent enthesitis. Innate IL-22 production promotes ileal tolerance.